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Beijnum, Judith Rosina van. "Gene expression profiling of tumor angiogenesis." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 2006. http://arno.unimaas.nl/show.cgi?fid=7710.
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Tan, Ern Yu. "Loss of protein folding gene expression in human tumors." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670106.
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Petty, Aaron. "Novel MIG-7 expression increases tumor cell invasion and tumor progression." Online access for everyone, 2008. http://www.dissertations.wsu.edu/Thesis/Spring2008/a_petty_040908.pdf.
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Askew, David. "Changes in macrophage functions and gene expression during tumor growth." Diss., This resource online, 1993. http://scholar.lib.vt.edu/theses/available/etd-05042006-164512/.
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Wykoff, Charles C. "The hypoxia-regulated transcriptome and its expression in cancer." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365288.
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Wang, Fuli. "Identification of tumor suppressor genes using the approach of gene inactivation test /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-798-7/.
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Clark, Aaron J. "The Expression and Function of Wilms' Tumor 1 in Malignant Glioma." VCU Scholars Compass, 2006. http://hdl.handle.net/10156/1665.
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Yamaga, Yuichi. "Gene expression profile of Dclk1+ cells in intestinal tumors." Kyoto University, 2019. http://hdl.handle.net/2433/236595.
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Karlgren, Maria. "Novel extrahepatic P450 enzymes with emphasis on the tumor specific CYP2W1 /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-139-5/.
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Kiss, Nimrod G. B. "DNA methylation and gene expression patterns in adrenal medullary tumors." Stockholm : Department of Molecular Medicin and Surgery, Karolinska Institutet, 2009. http://diss.kib.ki.se/2009/978-91-7409-750-4/.
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Gulyás, Miklós. "Mesothelial differentiation, mesothelioma and tumor markers in serous cavities /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-566-2/.
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Lodygin, Dmitri. "Epigenetic and pharmacological regulation of gene expression involved in senescence and tumor progression." [S.l.] : [s.n.], 2005. http://edoc.ub.uni-muenchen.de/archive/00004361.
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吳欲勳 and Yuk-fun Ng. "Regulation of mammary tumor cell cycle kinetics and gene expression bydietary fatty acids." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31219779.
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Howat, Sarah Lamont Telfer. "TSG6 : expression and influence on the stability of the extracellular matrix in joint tissues." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326100.
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Rodrigues, Amanda Teixeira. "Caracterização molecular e funcional de células de tumores adrenocorticais humanos." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-13112014-160412/.
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O Adenoma adrenocortical é frequente em adultos, já o carcinoma é raro e agressivo. Mesmo com critérios padronizados, ainda há dificuldade para diferenciar esses tumores, sendo necessário o estudo de marcadores eficientes na detecção e diferenciação. Por serem raros e com diversas manifestações clínicas, culturas in vitro pode ser uma ferramenta para o estudo de processos que envolvem a doença. Foi realizada a caracterização molecular e funcional de culturas de células de tumores de pacientes. Resultados de PCR Array não mostraram um padrão que diferenciasse as culturas em função dos diagnósticos. Desta análise, 7 oncogenes apresentaram maior expressão e 9 supressores de tumor apresentaram baixa expressão nas culturas. WWOX, FHIT e TP73 foram validados por qPCR e a sugestiva interação entre esses fatores nos tumores adrenocorticais merecem futuras investigações. O potencial funcional das culturas T83-ACC, T36-REC e T7-ACA(P) foram evidenciados, e mostraram que podem ser bons modelos para estudo da ação de hormônios e seus mecanismos.The adrenocortical adenoma is common in adults, since carcinoma is rare and aggressive. Even with standardized scores, it is still difficult to differentiate these tumors, the study of efficient markers in the detection and differentiation is necessary. Because they are rare and diverse clinical manifestations in vitro cultures can be a tool for the study of disease processes that involve. Molecular and functional characterization of cultured tumor cells of patients was conducted. PCR Array results did not show a pattern that differentiates cultures on the basis of diagnoses. This analysis showed higher expression 7 oncogenes and tumor suppressors 9 showed low expression in cultures. WWOX, FHIT and TP73 were validated by qPCR and suggestive interaction between these factors in adrenocortical tumors deserve further investigation. The functional potential of T83-ACC, T36-REC and T7-ACA(P) cell cultures were found, and shown confirm that they can be good models for studying the action of hormones and their mechanisms.
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Stoltzfus, Patricia. "Molecular markers reflecting malignant transformation and tumor progression /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-888-2.
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Vaarala, M. (Markku). "Differential gene expression in prostate cancer:identification of genes expressed in prostate cancer, androgen-dependent and androgen-independent LNCaP cell lines, and characterization of TMPRSS2 expression." Doctoral thesis, University of Oulu, 2000. http://urn.fi/urn:isbn:9514258304.
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Abstract
Prostate cancer is the most common solid tumor among men in Western industrialized countries. A major problem in
prostate cancer treatment is the development of androgen-independence, as androgen-deprivation therapy is the basic
therapy for the disease. Molecular mechanisms behind prostate cancer and androgen-independent growth development are
poorly known.
In this study, subtractive hybridization was used for the generation of a cDNA library specific for prostate cancer.
Analysis of the cDNA library revealed over-expression of several ribosomal proteins namely L4, L5, L7a, L23a, L30, L37,
S14 and S18, in prostate cancer cell lines. Over-expression of L7a and L37 was also confirmed in prostate cancer tissue
samples.
Further, cDNA array was used in order to examine differentially expressed genes in androgen-dependent and
androgen-independent prostate cancer cell line LNCaP. Monoamine oxidase A, an Expressed Sequence Tag (EST) similar to rat
P044, and EST AA412049 were highly over-expressed in androgen-dependent LNCaP cells. Tissue-type plasminogen activator,
interferon-inducible protein p78 (MxB), an EST similar to galectin-1, follistatin, fatty acid-binding protein 5, EST
AA609749, annexin I, the interferon-inducible gene 1-8U and phospholipase D1 were highly over-expressed in
androgen-independent LNCaP cells. The EST similar to rat P044, the EST similar to galectin-1, follistatin, annexin I and
the interferon-inducible gene 1-8U were also expressed in benign prostatic hyperplasia tissue. The Y-linked ribosomal
protein S4, Mat-8, and EST AA307912 were highly expressed in benign prostatic hyperplasia tissue.
In situ hybridization of mouse embryos and adult mouse tissues revealed the expression of TMPRSS2 in
the epithelium throughout the gastrointestinal, urogenital and respiratory tracts during development. In human multiple
tissue RNA dot blot, the highest level of expression was detected in prostate, and lower levels in colon, stomach and
salivary gland. TMPRSS2 transcript levels were significantly higher in prostate cancer tissue between benign and
malignant epithelium of prostate cancer patients with untreated disease. Similarly, in poorly differentiated
adenocarcinomas, expression in malignant tissue was significantly higher. Enzymatic mutation detection and direct
sequencing of TMPRSS2 coding region revealed only one deletion in aggressive disease among 9 non-aggressive and 9
aggressive prostate cancer samples. No other mutations were found. Detected 7-base pair deletion leads to premature stop
codon and disruption of serine protease substrate binding and catalytic active site.
We cloned several potential genes whose expression is changed during prostate cancer initiation or progression. These
genes may serve as prostate cancer markers, and further studies are needed to clarify the expression of these proteins
during the disease.
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PENG, LI. "Gene Expression Study and DNA Methylation Status of Aryl Hydrocarbon Receptor Gene in Rbf/f;Alb-Cre+ Mouse Liver Tumors." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1186635329.
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Wang, Ying. "Drg-1 suppresses tumor metastasis by down-regulating the expression of the ATF3 gene /." Available to subscribers only, 2005. http://proquest.umi.com/pqdweb?did=1075682441&sid=34&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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Thesis (M.S.)--Southern Illinois University Carbondale, 2005."Department of Molecular Biology, Microbiology and Biochemisty." Includes bibliographical references (leaves 50-61). Also available online.
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Branham-O'Connor, Melissa. "Gene expression profile of tumor cell-fused or Noni (Morinda citrifolia)-treated dendritic cells." Connect to this title online, 2009. http://etd.lib.clemson.edu/documents/1263398967/.
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Ng, Yuk-fun. "Regulation of mammary tumor cell cycle kinetics and gene expression by dietary fatty acids /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19471026.
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Bandapalli, Obul Reddy. "Analysis of global gene expression profiles and invasion related genes of colorectal liver metastasis." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15710.
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Die Leber ist das am häufigsten von Metastasen betroffene Organ und kann daher als Modellorgan für metastatische Invasion dienen. Aus diesem Grund war es das Ziel dieser Dissertation Genexpressionsprofile zu verstehen und metastasierungs- sowie invasionsassoziierte Gene zu identifizieren. Differentielle Genexpression wurde in drei Systemen überprüft: Einem syngenen Mausmodell, einem Xenograftmodell sowie in fünf Gewebeproben von Patienten. Genexpressionprofile des syngenen Mausmodells und der Patientenproben zeigten, dass man die Invasionsfront als Ganzes betrachten, um möglichst viele über-lappende Gene zu finden. Globale Genexpressionstudien, die auf den Wirtsteil der Invasionsfront zeigten bemerkenswerte Überrepräsentation z. B. der „GO-terms“ „extrazelluläre Matrix“, Zellkommunikation“, „Antwort auf biotischen Stimulus“, Strukturmolekülaktivität“ und „Zellwachstum“. Marker der Aktivierung hepatischer Sternzellen überrepräsentiert in der invasionsfront, was die Durchführbarkeit einer Analyse differentieller Genexpression im genomweiten Rahmen anzeigt. Globale Genexpressionsstudien, auf den Tumorzellen in der in vitro Situation, in vivo und in der Invasionsfront zeigten insgesamt einen Anstieg zellulärer Spezialisierung von der in vitro zur Invasionsfront. Sezernierte proangiogenetische Chemokine zeigten eine Hochregulation in der Invasionsfront. Das beta catenin Gen war in der Invasionsfront 9.6 fach erhöht im Vergleich zur in vitro Situation. Die Überprüfung der transkriptionellen Aktivierung von beta catenin über die Prüfung der Promotoraktivität zeigte einen 18.4 fachen Anstieg in den Tumorzellen der Invasionsfront. Weiterhin war die Promotoraktivität (an Hand der Aktivität der mRNA des Alkalischen Phosphatase Reportergens) im Tumorinneren 3.5 fach höher als in der Zellkultur, was für einen transkriptionellen Mechanismus der beta catenin Regulation zusätzlich zu den posttranslationalen Mechanismen spricht.Liver is most frequently populated by metastases and may therefore serve as a model organ for metastatic invasion. So the aim of this thesis is to understand the gene expression profiles and identify metastasis and invasion related genes. Differential gene expression was examined in three systems: A syngeneic mouse model, a xenograft model and five clinical specimens. Gene expression profiles of a syngenic mouse model and human clinical specimen revealed that the invasion front should be considered as a whole to find more overlapping potential target genes. Global gene expression studies on the host part of the invasion front, revealed a pronounced overrepresentation of GO-terms (e.g. “extracellular matrix”, “cell communication”, “response to biotic stimulus”, “structural molecule activity” and “cell growth”). Hepatic stellate cell activation markers were over-represented in the invasion front demonstrating the feasibility of a differential gene expression approach on a genome wide scale. Global gene expression studies of the tumor cells in vitro, in vivo and tumor part of the invasion front revealed an overall increase of cellular specialization from in vitro to the invasion front. Secreted angiogenic cytokines were found to be up regulated in the invasion front. Beta catenin gene of “cell adhesion” GO term was elevated 9.6 fold in invasion front compared to in vitro. Evaluation of transcriptional up-regulation of beta catenin by promoter activity showed an 18.4 fold increase in the tumor cells of the invasion front as compared to those from the faraway tumor. Promoter activity assessed by soluble human placental alkaline phosphatase reporter gene mRNA was 3.5 fold higher in the inner parts of the tumor than in vitro cells indicating a transcriptional mechanism of beta catenin regulation in addition to the posttranslational regulatory mechanisms.
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Certel, Seçil Güneş Hatice. "Expression Profiles Of Differentially Expressed Genes Of Rat Mammary Adenocarcinoma In Various Tumor Cell Lines And Effects Of Some Antioxidants/." [s.l.]: [s.n.], 2005. http://library.iyte.edu.tr/tezler/master/biyoteknoloji/T000334.pdf.
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Foukakis, Theodoros. "Basic and translational studies of follicular thyroid neoplasia /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-319-1/.
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Avik, Joonas. "Deciphering mechanisms underlying tumor heterogeneity using Multi-Omics approaches." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-278700.
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Cancer is a complex disease and presents one of the greatest challenges in modern medicine. Despite remarkable advances in treatment of several cancer types, relapse and resistance to therapy remain recurring outcomes in patients, which underscores a need for personalized treatment approaches. These complications have been related to the high genetic diversity observed within tumors, termed intratumor heterogeneity (ITH). While specific mutational profiles have been associated with the development of heterogeneous tumors, the relationship between ITH and phenotype could unveil features that undergo selection and convey fitness. Features presented in the transcriptome, as markers of heterogeneity, might therefore be valuable biomarkers. In this project, these features are explored by assuming a linear relationship between genetic ITH measures and gene expression data from The Cancer Genome Atlas samples. By first reducing the number of variables among the transcriptome to the differentially expressed genes between low and high ITH samples, the association between specific gene expression profiles and ITH is sought with a linear model. By using two different methods for estimating ITH, called Expands and PhyloWGS, the association was modeled with each method. Interestingly, the model based on Expands captured the elevated expression of a chaperone gene DNAJC18 as being consistently associated with lower ITH in four cancer types. On the other hand, models based on PhyloWGS presented lower predictive power. These results demonstrate that the transcriptome can be used to predict genetic ITH, although this depends on the method used for characterizing ITH.Cancer är en komplex sjukdom och en av de största utmaningarna i dagens medicin. Trots stora framsteg i behandlingen av flera cancerformer är återfall och terapiresistens återkommande problem vilket talar starkt för behov av individualiserad behandling. Dessa komplikationer har relaterats till den höga genetiska variabiliteten som observeras inom tumörer, även kallad intratumoral heterogenitet (ITH). Undersökning av relationen mellan ITH och fenotypisk data kan ta fram markörer som är involverade i cancerutvecklingen som bidragare till heterogenitet. Genom att modellera associationen mellan transcriptomen och ITH kan man även hitta kliniskt relevanta biomarkörer. I detta projekt undersöks relationen mellan genutryck och ITH genom att applicera linjär regression. Genom att först reducera antalet variabler i transkriptomen till de diferentiellt utryckta gener, används linjära modellen för att ta fram specifika gener vars utryck kan relateras till ändringar i ITH uppskattad för The Cancer Genome Atlas prover. ITH uppskattas med två algoritmiska metoder, kallade Expands och PhyloWGS. Resultaten visade att förhöjd uttryck an genen DNAJC18 är associerad med lägre ITH uppskattad med Expands bland fyra cancer typer. Trots detta visade inte genutryck och ITH uppskattat med PhyloWGS lika starkt linjärt samband.
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Poulin, Louise. "Expression differentielle du produit du gene 'src' dans les tumeurs induites par le virus de sarcome aviaire = Differential expression of the 'src' gene product in tumor cells induced by avian sarcoma virus." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=74020.
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Hamm, Christopher Allan. "Functional genomic analyses of the impact of global hypomethylation and of tumor microenvironment in a rat model of human chondrosarcoma." Diss., University of Iowa, 2009. https://ir.uiowa.edu/etd/372.
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Chondrosarcomas are malignant cartilage tumors that do not respond to traditional chemotherapy or radiation. The 5-year survival rate of histologic grade III chondrosarcoma is less than 30%. To achieve a greater understanding of chondrosarcoma tumorigenesis, a model for human chondrosarcoma has been established in a rat system. The model, known as the Swarm rat chondrosarcoma (SRC), resembles human chondrosarcoma and provides a system to study tumor growth and progression. Here we examined the influence of the tumor microenvironment and the impact of genome-wide hypomethylation on the behavior of SRC tumors, two factors known to contribute fundamentally to the development and progression of solid tumors.
Previous studies with SRC revealed that tumor microenvironment can significantly influence chondrosarcoma malignancy, but the underlying biologic mechanisms have not been defined. To address this issue we carried out epigenetic and gene expression studies on the SRC tumors that were initiated at different transplantation sites. The epigenetic analysis revealed that microenvironmental changes could promote global DNA hypomethylation in SRC cells. Subsequent gene expression analyses revealed that the transplantation site had a significant impact on the gene expression profiles of SRC tumors. These SRC tumors had unique gene expression profiles, and we were able to identify genes that were differentially expressed between SRC tumors originating from different transplantation sites. Functional analyses of two differentially expressed genes, thymosin-beta-4 and c-fos, provided insight into the role that these genes may play in the development and progression of chondrosarcoma.
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Foerster, Susann. "Gene expression profiling of human lymph node-positive gastric adenocarcinomas." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://dx.doi.org/10.18452/16259.
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In dieser Arbeit wurden Genexpressionsprofile diffuser und intestinaler Magenadenokarzinome mittels Microarray-Technik erstellt. Der intestinale Typ konnte als stark proliferierender Tumor mit signifikanter Überexpression von zellzyklusrelevanten Genen definiert werden, während der diffuse Typ als stark stromaabhängig mit signifikanter Überexpression von Genen der extrazellulären Matrix hervortrat. Thrombospondin 4 (THBS4) wurde dabei als das am stärksten differentiell exprimierte Gen identifiziert, wobei seine mRNA in diffusen Tumoren eminent überexprimiert wird. Immunhistochemische Studien bestätigten diese starke Überexpression auf Proteinebene und zeigten, dass THBS4 eine übermäßig angereicherte extrazelluläre Komponente des Tumorstromas ist. Kolokalisierungsstudien zeigten zudem, dass THBS4-positive Zellen auch positiv für Vimentin und Smooth muscle actin (alpha) sind. Diese Ergebnisse belegen, dass THBS4 von Tumor-assoziierten Fibroblasten (TAF) exprimiert wird. Dies konnte durch zusätzliche in vitro Experimente bestätigt werden, die aufzeigten, dass TAF von diffusen Tumoren eine stärkere THBS4-mRNA Expression aufweisen als normale Fibroblasten des Magens. Abschließend konnten in vitro Kokultur-Studien aufdecken, dass die THBS4-Expression in Fibroblasten durch Tumorzellen diffuser Magentumore transkriptionell stimuliert wird. Metastasenbefall regionaler Lymphknoten (N+) ist bei den meisten Magenadenokarzinomdiagnosen bereits vorhanden. Dieser ist der stärkste derzeit verfügbare Parameter zur Abschätzung der Prognose, reicht aber für eine eindeutige Vorhersage nicht aus. Um ergänzende molekulare Prognoseindikatoren zu identifizieren, wurden aus den Microarray-Daten Gene, deren Expression mit dem klinischen Verlauf von N+ Patienten korreliert, extrahiert. Einige dieser Gene, z.B. RAN binding protein 17 und ras-related associated with diabetes, konnten mittels quantitativer real-time PCR als Marker für verkürztes progressionsfreies Überleben validiert werden.In this work, gene expression profiles of diffuse and intestinal-type gastric adenocarcinomas were established using the microarray technique. The intestinal type was identified to be a highly proliferative entity with significant overexpression of cell cycle-relevant genes, whereas the diffuse type was proven to be strongly stroma-dependent with significant overexpression of extracellular matrix genes. Thrombospondin 4 (THBS4) was identified as the gene most differentially expressed between the two types with vast mRNA overexpression in diffuse-type tumors. Immunohistochemical studies proved overexpression on protein level and elucidated that THBS4 is a heavily accumulated extracellular constituent of the tumor stroma. Colocalization studies uncovered that THBS4-positive cells are also positive for vimentin and alpha-smooth muscle actin. These data signify that THBS4 is expressed by subpopulations of cancer-associated fibroblasts (CAFs). This was further evidenced by in vitro experiments demonstrating that THBS4 mRNA expression is increased in CAFs of diffuse-type tumors compared to normal gastric fibroblasts. Finally, in vitro coculture studies revealed that transcriptional THBS4 expression in fibroblasts is stimulated by diffuse-type gastric tumor cells. Metastatic involvement of regional lymph nodes (N+) usually accompanies diagnosis of gastric adenocarcinoma and is currently considered the most important parameter for assessment of prognosis. However, estimation of prognosis based on this parameter alone is not sufficiently reliable. In order to identify additional molecular prognosis markers, genes whose expression correlates with clinical outcome of N+ patients were extracted from the microarray data. Via quantitative real-time PCR, several genes, e.g. RAN binding protein 17 and ras-related associated with diabetes, were successfully validated to allow an expression-based stratification of patients with respect to disease-free survival.
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Cunha, Bianca Rodrigues da. "Investigação do perfil de expressão gênica e protéica de componentes do microambiente tumoral." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/41/41131/tde-02042012-110841/.
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Tem se tornado evidente que a iniciação e a progressão do câncer depende de vários componentes do microambiente tumoral, incluindo células inflamatórias e imunes (linfócitos, macrófagos e mastócitos), fibroblastos, células endoteliais, adipócitos e matriz extracelular. De maneira geral, esses componentes são conhecidos como estroma. Tanto interações pró- como anti-tumor ocorrem entre um câncer e suas células vizinhas. Em um estudo prévio, avaliamos dados de bibliotecas SAGE de carcinoma epidermóide de cabeça e pescoço (CECP) usando ferramentas estatísticas e de bioinformática e pudemos identificar os genes mais e menos expressos em tumores metastáticos versus não metastáticos e em tumores versus tecidos normais. Em outro estudo, avaliamos fatores parácrinos solúveis produzidos por células do estroma e por células neoplásicas que poderiam influenciar proliferação e expressão gênica e protéica. Ambos os estudos identificaram marcadores potenciais associados a respostas inflamatórias ou imunes. Dezenove desses genes foram selecionados por PCR em tempo real e o estudo foi realizado nas linhagens SCC-9 de células epiteliais neoplásicas e de fibroblastos isolados de um câncer oral, e em 40 amostras de carcinomas primários de cabeça e pescoço (6 amostras micro e 34 macrodissecadas). Nós também utilizamos eletroforese unidimensional para analisar a expressão protéica nesse conjunto de amostras. Como a microdissecção produziu baixas concentrações de RNA e proteínas, ciclos extras de amplificação de mRNA foram necessários para obter material suficiente para experimentos de PCR. Nossos dados mostraram que os perfis de expressão foram provavelmente pouco preservados durante os ciclos extras de amplificação. Em amostras macrodissecadas, nós consistentemente observamos que o nível de transcritos de MGLL, COX2, EP3, EP4 e LTAH4 estava reduzido, porém presente nas suas margens cirúrgicas. Os dados não confirmaram, em células de CECP, a hipótese de que MGLL produz menssageiros lipídicos oncogênicos, esta via pode não atuar nesses pacientes. Nós também observamos que metaloproteinases são expressas em níveis elevados em CECP e devem estar envolvidas na degradação da matriz extracelular. Células neoplásicas e do estroma desses carcinomas exibem uma ampla variedade de proteínas com níveis muito diferentes de expressão. Este resultado abre perspectivas para realização de experimentos de validaçãoIt has become evident that cancer initiation and progression depends on several components of the tumor microenvironment, including inflammatory and immune cells (lymphocytes, macrophages and mastocytes), fibroblasts, endothelial cells, adipocytes, and extracellular matrix. Collectively, these components are known as the stroma. Both pro- and anti-tumor interactions occur between a tumor and its surrounding cells. In a previous study, we evaluated data from SAGE libraries of head and neck squamous cell carcinoma (HNSCC) using statistical and bioinformatic tools and we could identify top-up and top-downregulated genes in metastatic versus non-metastatic tumors and in tumors versus normal tissues. In another study, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression. Both studies identified potential markers associated with immune or inflammatory response in head and neck tumorigenesis. Nineteen of these genes were selected for real-time polymerase chain reaction (PCR) and the study was carried out on the epithelial cancer cell line SCC-9 and on fibroblasts isolated from an oral cancer, and in 40 samples from primary HNSCC (6 micro and 34 macrodissected samples). We also used one-dimensional gel electrophoresis and mass spectrometry to analyze protein expression in this set of samples. As microdissection yielded low RNA and protein concentrations, extra rounds of mRNA amplification were necessary to obtain sufficient material for PCR experiments. Our data showed that expression profiles were probably scantily preserved during the extra rounds of amplification. In macrodissected samples, we consistently observed that the level of MGLL, COX2, EP3, EP4 e LTAH4 transcripts was low in most tumors but present in their surgical margins. The data do not confirm in HNSCC the hypothesis that MGLL produces oncogenic lipid messengers, this pathway may not act in these patients. We also observed that metalloproteinases are overexpressed in HNSCC and should be involved in extracellular matix degradation. Neoplastic and stromal cells from HNSCC exhibit a wide variety of proteins with very different levels of expression. This result opens the perspective to perform validation experiments.
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Rachfal, Amy Wilson. "Expression and actions of connective tissue growth factor." The Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1069791086.
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Scian, Mariano J. "MODULATION OF GENE EXPRESSION BY TUMOR-DERIVED MUTANT p53. ROLE OF TRANSACTIVATION IN GAIN-OF-FUNCTION." VCU Scholars Compass, 2005. https://scholarscompass.vcu.edu/etd/5518.
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It was hypothesized that the C-terminal sequences for mutant p53 would be required for oligomerization. and oligomerization may be critical for gain-of-function. An N-terminal deletion mutant of p53 that deletes amino acids 1-293 was used as a tool to perform hetero-oligomerization studies. This mutant retains the entire oligomerization domain but dispenses off the transactivation domain and a large portion of the sequence- specific DNA-binding domain. Co-transfection experiments show that p53 del. 1-293 forms hetero-oligomeric complexes with p53-D281G. Also. co-expression of p53 del. 1- 293 with p53-D281G inhibited p53-D28lG-mediated transactivation of the EGFR and MDRl promoters suggesting that hetero-oligomerization inactivates transcriptional functions of mutant p53. The interaction of p53 deli 1-293 and p53-D281G reduced transactivation potential of p53-D281G in stably transfected 10(3) murine cells. Therefore, the data presented supports the idea that proper oligomeric forms of mutant p53 are required for its transactivation function. Expression of mutant p53-D2810 also resulted in increased growth rate (H1299 cells), decreased chemosensitivity (H1299 and 21PT cells) and increased plating efficiency (Saos-2 cells). Expression of a transactivation deficient mutant p53 did not induce gain-of-function properties (increased growth rate and decreased chemosensitivity). Unlike the other gain-of-function properties tested, soft agar plating efficiency in Saos-2 cells was not significantly affected by the expression of a transactivation deficient mutant p53, suggesting that transactivation may not be the only factor affecting this gain-of-function property In order to identify the genes responsible for the observed phenotypes, global gene expression analyses were carried out using p53-null H1299 cell stably transfected to express mutant p53 (-Rl75H, -R273H and -D281G). A thorough and stringent analysis revealed 150 genes up-regulated by the expression of mutant p53. Up-regulation of a number of these genes was confirmed by QPCR and transient transcriptional promoter analyses; expression of the transactivation deficient mutant p53-D2810 (L22Q/W23S) did not result in up-regulation of the tested genes further supporting the idea that transactivation of genes is directly related to gain-of-function phenotypes. Using the ASNS gene as a model, this transactivation by mutant p53 was concentration dependent and that the increased transcription did indeed result in increased protein levels.
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Samuel, Shaija. "Studies on gene expression profiling in JB6 cells susceptible and resistant to tumor promoter induced neoplastic transformation and regulation of gene expression at the AP-1 DNA binding site." Texas A&M University, 2004. http://hdl.handle.net/1969.1/2538.
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Gene expression underlies all important biological processes in a cell and mis-regulated gene expression plays a causal or contributory role in several diseases including cancers. Towards identifying molecular determinants that confer susceptibility and resistance to tumor promoter induced neoplastic transformation, we analyzed the gene expression profile differences among tumor promoter TPA treated and untreated mouse epidermal JB6 cells by means of cDNA microarray analyses. The expression patterns for several genes were validated by real time PCR analyses. Seventy-four genes belonging to six functional categories were found to be differentially expressed. Data from this study implicate pathways which mediate cell adhesion, migration and interferon signalling, tumor suppressors, apoptotic proteins and transcription factors and includes twenty-six genes whose involvement has not been previously implicated in cancer.
In a second study we used a DNA affinity chromatography based assay to purify two proteins that bound specifically to the AP-1 DNA binding site. Analyses of the purified proteins by mass spectrometric sequencing determined the identities of these proteins as nucleolin and Y-box binding protein 1 (YB-1). We tested the hypothesis that these proteins regulate transactivation at the AP-1 site. Overexpression of nucleolin and YB-1, both alone or in combination, repressed AP-1 dependent gene transactivation. To understand the mechanism of transrepression, we analyzed whether nucleolin and/or YB-1 affected the levels and/or disrupted the intracellular localization of the AP-1 protein subunits. Western blot analyses of all the AP-1 subunits revealed that the levels of AP-1 were unaffected. Cell fractionation confirmed that the AP-1 levels were not altered in the nuclear or cytoplasmic compartments. We further tested the hypothesis that nucleolin and YB-1 repressed AP-1 transactivation by competing with AP-1 proteins for the AP-1 site. The results from this experiment were inconclusive and the precise mechanism of repression is currently under investigation.
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Martins, Claudia Maria de Oliveira 1961. "Expression of the metastasis suppressor gene KISS1 in uveal and cutaneous melanoma." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116098.
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Uveal Melanoma (UM) is the most common malignant intra-ocular tumor in adults. Forty-five percent of UM patients develop metastasis within fifteen years of the initial diagnosis. Cutaneous Melanoma (CM) is a highly metastatic cancer that accounts for the majority of skin cancer deaths. Current treatments are not especially effective for the metastatic phase of the disease. Therefore, the identification of new molecular targets that can be exploited in the clinic are needed.KISS1 is a putative human metastasis suppressor gene. The purpose of this study was to investigate the expression of KISS1 in melanoma and its potential value as a prognostic marker.
From results in vitro and in vivo we were able to characterize KISS1 in UM for the first time as well as its expression at the protein level, in CM. The correlation between KISS1 expression and UM survival rate suggests an important role for KISS1 as a prognostic marker in this tumor.
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Halstead, Bartley W. "Effect of dietary fatty acids on the expression of the Fgf-3 gene and mouse mammary tumor virus in strain A/St mammary tumors." Virtual Press, 1997. http://liblink.bsu.edu/uhtbin/catkey/1041900.
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The specific objective of this study was to determine if Fgf-3 gene expression is mediated by dietary fatty acids and to confirm mouse mammary tumor virus infection. It is well known that dietary linoleic acid enhances growth and dietary stearic acid inhibits growth of mammary tumors. Tumor RNA was extracted from female strain A/St mice fed one of four diets. A radioactively labeled anti-sense RNA probe was generated, invitro, from isolated and purified pFgf-3c (int-2c clone contained in the vector pSP65). The Fgf-3c probe was hybridized to extracted tumor RNA using the ribonuclease protection assay.Electron microscopy confirmed MMTV infection by visualization of type A and B particles in tumor tissue. Expression of Fgf-3c, qualified by RNase protection assay, ranged from 0.02 to 5.89 (relative band density) in all of the diet groups. A positive association between Fgf-3c expression and weight was observed among the tumors of the SA-1 diet (R = 0.947). The SF, SF-1, and PA experimental diets, individually, did not appear to show strong correlation with respect to tumor size. Fgf-3 expression was less in small tumors (<275 mg) and enhanced in large tumors (>275 mg) (p<0.05).Department of Biology
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Karimi, Mahdad. "Functional analysis of the -308G/A polymorphism in the tumour necrosis factor promoter." University of Western Australia. School of Biomedical, Biomolecular and Chemical Sciences, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0140.
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[Truncated abstract] Tumor Necrosis Factor (TNF) is a potent pro-inflammatory cytokine involved in a range of biological functions including the differentiation, proliferation and survival of many cell types. The TNF gene lies in the class III region of the major histocompatibility complex (MHC), approximately 250 Kbp centromeric of the HLA-B locus and 850 Kbp telomeric of HLA-DR. Due to the genomic location and biological relevance of TNF, it is thought that genetic heterogeneity at this locus may be associated with autoimmune and infectious diseases. A G-to-A single nucleotide polymorphism (SNP) at position -308 (relative to the transcriptional start site) in the TNF promoter has been well described. The less common -308A variant has been shown to be linked with the HLA-A1, B8, DR3 haplotype which in turn has been associated to a high TNF producing phenotype. Determining whether the -308 polymorphism contributes to elevated levels of expression has therefore been a priority for many research groups. Some investigators have shown differences in transcription between the -308G and -308A alleles while others could not. These contradicting results have led to conflicting views regarding the functional relevance of the -308 SNP. In this study, statistical analysis of 18 independent transient transfections of -308 biallelic TNF reporter constructs have provided evidence for a functional consequence of the polymorphism. ... In addition, chromatin accessibility of this region was maximal at greater levels of transcription suggesting a role for both chromatin structure and YY1 binding in -308G regulation. Surprisingly, chromatin structure did not seem to play a role in -308A regulation nor was there any significant binding of YY1, suggesting the -308 region does not affect transcriptional control of TNF. Taken as a whole, the G-to-A SNP relieves YY1 binding and demonstrates an allele-specific regulatory mechanism controlling expression. A growing list of promoter polymorphisms exists in the human genome having associations with certain diseases. Determining the functional consequence of these SNPs has proven difficult and utilized mainly in vitro approaches. In this thesis, a unique approach to investigating the functionality of promoter polymoprhisms has been developed, utilizing in vivo techniques which test their effects in a more natural system. It is hoped that the identification of the allele-specific YY1-mediated control of the -308 region of the TNF promoter may provide insight into overexpression as a consequence of the polymorphism and its role in the genetic susceptibility to MHC-associated autoimmune disease.
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Sun, Zhongke [Verfasser]. "Development of gene expression systems in Bifidobacterium bifidum S17 and their application for tumor therapy / Zhongke Sun." Ulm : Universität Ulm. Fakultät für Naturwissenschaften, 2014. http://d-nb.info/1062611020/34.
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Vaitkienė, Grigaitė Paulina. "A study of tumor suppressor gene expression and promoter methylation for the identification of prognostic markers in glioblastoma." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2013. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2013~D_20130419_111627-63926.
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Glioblastoma (GBM) is the most common primary brain tumor in adults. This study attempted to
identify the genes potentially regulated by promoter methylation in GBM. Therefore, we analyzed
the expression of COX7A1, SPINT1, AREG, NPTX2, and KRT81 in glioblastomas and human brain
tissue and investigated if there were any associations between the expression and methylation of
these genes. Moreover, we aimed to determine the methylation frequency of 11 genes (AREG,
CASP8, CD81, DcR1, DR4, GATA4, GATA6, hMLH1, NPTX2, TES, and TFPI2) promoters in 100
patients with glioblastoma multiforme and to evaluate the associations between patients’ clinical
characteristics and prognostic value. The methylation status of the following 4 gene promoters
was significantly related to patients’ survival after surgery: AREG, CASP8, GATA6 and TFPI2.
Identification of the methylation status of these genes could be one of the objective criteria in the
prognosis of disease course in patients with glioblastoma and could supplement the list of already
known epigenetic markers. The methylation status of a combination of 6 genes (AREG, CASP8,
DR4, GATA4, GATA6, and TFPI2) was found to be a more accurate independent prognostic factor
associated with patients’ survival after surgery when compared with the methylation status of
individual genes. The molecular classification of GBM according to the methylation profile of a
combination of these 6 genes could help clinicians tailor an appropriate treatment... [to full text]Glioblastoma (GBM) yra vienas labiausiai paplitusių ir agresyviausių pirminių galvos smegenų auglių. Siekiant nustatyti molekulinius žymenis, susijusius su GBM vystymusi, diagnoze ir prognoze, buvo atlikta 14 genų (AREG, CASP8, CD81, COX7A1, DcR1, DR4, GATA4, GATA6, hMLH1, KRT81, NPTX2, SPINT1, TES ir TFPI2) promotorių metilinimo analizė. Buvo nustatyti naviką slopinančių genų promotorių metilinimo dažniai, ryšiai su klinikinėmis sergančiųjų GBM charakteristikomis ir prognozinė vertė. Disertacinio darbo metu nustatyta, kad AREG ir NTPX2 genų raiška susijusi su šių genų promotorių metilinimu, tuo tarpu COX7A1, KRT81 ir SPINT1 genų raiškos skirtumai nėra susiję su šių genų promotorių metilinimu. Naujų epigenetinių žymenų tyrimai 100 GBM pavyzdžių parodė navikų epigenetinį heterogeniškumą ir įvairų tirtų genų promotorių metilinimo dažnį. Nustatyta, kad AREG, CASP8, GATA6 ir TFPI2 genų promotorių metilinimas statistiškai patikimai susijęs su išgyvenimo trukme po operacijos. Šių genų promotoriaus metilinimo nustatymas gali būti vienas iš objektyvių kriterijų prognozuojant pacientų ligos eigą ir papildyti jau nustatytų epigenetinių žymenų sąrašą. Buvo sudarytas, suminis šešių genų (AREG, CASP8, DR4, GATA4, GATA6 ir TFPI2) derinys, kuris yra tikslesnis nepriklausomas prognozinis veiksnys, susijęs su išgyvenimo trukme po operacijos lyginant su atskirų genų promotorių metilinimu. GBM molekulinis tipavimas pagal šių šešių genų derinį galėtų padėti parenkant gydymo strategiją.
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Farrow, Michael John. "The effect of androstenediol on gene expression and NF-kappaB activation in vitro." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1187109346.
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Abreu, Nayara Pereira de. "Análise da expressão do fator de transcrição Sf-1 e sua regulação em culturas primárias de adrenal de rato: o papel de Pod-1/TCF21." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/42/42131/tde-14032014-092736/.
Full textAbstract:
O fator esteroidogênico 1 (SF-1) é um fator de transcrição envolvido no desenvolvimento, na produção de esteroides e na proliferação do córtex adrenal. POD-1/TCF21 parece estar envolvido na regulação de SF-1, inibindo sua expressão e suas funções nas células esteroidogênicas. No entanto, a expressão e a relação entre SF-1 e POD-1 em células normais adrenocorticais não está esclarecida. O objetivo desse trabalho foi determinar se Pod-1 regula a expressão de Sf-1 através da hiperexpressão de Pod-1 em culturas primárias de células adrenocorticais de rato. Foi analisada a expressão endógena de Sf-1 e Pod-1, através da reação de RT-PCR quantitativo, em células glomerulosas (G) e células fasciculadas/reticulares (F/R), bem como em células transfectadas com pCMVMycPod-1. Os resultados mostraram que Sf-1 está mais expresso nas células F/R do que nas células G e ambos os tipos celulares apresentaram baixa expressão endógena de Pod-1. As células F/R transfectadas apresentaram um aumento estatisticamente significante da expressão de Sf-1, mas não as células G. Esses resultados sugerem um mecanismo de ação de Pod-1 no controle da expressão de Sf-1 em células adrenocorticais normais distinto do descrito em células de tumores adrenais e células esteroidogênicas.The steroidogenic factor 1 (SF-1) is a transcription factor involved in the development, steroids production and adrenal cortex proliferation. There are evidences that suggest that POD-1/TCF21 may be involved in the inhibition of SF-1 and modulating the SF-1 function in steroidogenic cells. However, the expression and the relation between SF-1 and POD-1 in normal adrenocortical cells are still unclear. The aim of this study was to determine whether Pod-1 regulates the expression of Sf-1 by overexpression of Pod-1 in primary cell cultures of rat adrenal cortex. We analyzed the expression of endogenous Sf-1 and Pod-1 by RT-PCR quantitative in glomerulosa (G) and fasciculata/reticularis (F/R) cells and also in cells transfected with plasmid CMVMycPod-1. The results showed that the SF-1 expression is higher in F/R cells than the G cells. Moreover, both cell types showed low endogenous expression of Pod-1. Analysis of Sf-1 expression in transfected cells showed a statistically significant increase in the Sf-1 expression in F/R cells but not in G cells. These results suggest a mechanism of action of Pod-1 in the regulation of Sf-1 in normal cells distinct of described in adrenocortical tumor cells and other steroidogenic cells.
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Åstrand, Carolina. "Chromatin structure and histone modifications in gene regulation /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-989-0/.
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Luna, Brenda. "Prenatal Environmental Exposure and Neurodevelopmentally Important Gene Expression in Malformed Brain Tissue from Pediatric Intractable Epilepsy Patients." FIU Digital Commons, 2011. http://digitalcommons.fiu.edu/etd/445.
Full textAbstract:
The primary objective of this proposal was to determine whether mitochondrial oxidative stress and variation in a particular mtDNA lineage contribute to the risk of developing cortical dysplasia and are potential contributing factors in epileptogenesis in children. The occurrence of epilepsy in children is highly associated with malformations of cortical development (MCD). It appears that MCD might arise from developmental errors due to environmental exposures in combination with inherited variation in response to environmental exposures and mitochondrial function. Therefore, it is postulated that variation in a particular mtDNA lineage of children contributes to the effects of mitochondrial DNA damage on MCD phenotype. Quantitative PCR and dot blot were used to examine mitochondrial oxidative damage and single nucleotide polymorphism (SNP) in the mitochondrial genome in brain tissue from 48 pediatric intractable epilepsy patients from Miami Children’s Hospital and 11 control samples from NICHD Brain and Tissue Bank for Developmental Disorders.
Epilepsy patients showed higher mtDNA copy number compared to normal health subjects (controls). Oxidative mtDNA damage was lower in non-neoplastic but higher in neoplastic epilepsy patients compared to controls. There was a trend of lower mtDNA oxidative damage in the non-neoplastic (MCD) patients compared to controls, yet, the reverse was observed in neoplastic (MCD and Non-MCD) epilepsy patients. The presence of mtDNA SNP and haplogroups did not show any statistically significant relationships with epilepsy phenotypes. However, SNPs G9804A and G9952A were found in higher frequencies in epilepsy samples. Logistic regression analysis showed no relationship between mtDNA oxidative stress, mtDNA copy number, mitochondrial haplogroups and SNP variations with epilepsy in pediatric patients. The levels of mtDNA copy number and oxidative mtDNA damage and the SNPs G9952A and T10010C predicted neoplastic epilepsy, however, this was not significant due to a small sample size of pediatric subjects. Findings of this study indicate that an increase in mtDNA content may be compensatory mechanisms for defective mitochondria in intractable epilepsy and brain tumor. Further validation of these findings related to mitochondrial genotypes and mitochondrial dysfunction in pediatric epilepsy and MCD may lay the ground for the development of new therapies and prevention strategies during embryogenesis.
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Forsberg, Lars. "Localization and characterization of genes involved in parathyroid tumor development /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-476-3/.
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Severmann, Julia [Verfasser], and Peter A. [Akademischer Betreuer] Horn. "Cell cycle-dependent gene expression by Mybl2 - a tumor suppressor in MDS / Julia Severmann ; Betreuer: Peter A. Horn." Duisburg, 2018. http://d-nb.info/1161341358/34.
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Tsang, Tom Chun-Chang. "Viraljun oncogene serves as a suppressor of phorbol ester TPA induced tumor cell invasion and stromelysin gene expression." Diss., The University of Arizona, 1994. http://hdl.handle.net/10150/186681.
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Carcinogenesis in the mouse skin is a multistep process involving initiation, promotion, and progression. In order for the benign papilloma cells that have been initiated and promoted to become malignant, genetic alterations are believed to be involved. The viral jun (v-jun) oncogene encodes a transcription factor that can participate in the transactivation of genes through the AP-1 complex. Evidence indicates that the ability of v-jun to transform cells and stimulate transcription depends on the cell type. The question that I have attempted to answer in my dissertation studies is whether expression of the v-jun gene in benign tumor forming mouse keratinocytes that already express an activated c-rasᴴᵃ oncogene would cause malignant progression. Our results showed that the v-jun transfection did not result in malignant progression; instead, we made the unexpected observation that the ability of these cells to invade reconstituted basement membrane matrix (in vitro) in response to the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was suppressed. This phenomenon could partially be explained by the suppression of the induction by phorbol ester of expression of the metalloproteinase, stromelysin (transin). Of interest was the finding that TPA induction of other cellular genes known to be regulated by AP-1 was not inhibited in the benign tumor cells expressing v-jun. The suppressor activity shown by v-jun is different than that of other tumor suppressor genes in that it appears to be specific for the process of tumor invasion. A potential implication of this unexpected finding is that it may provide insight on how to develop cancer therapeutic strategies that can specifically inhibit tumor invasion. I have constructed a set of cassette cloning vectors that can be used for rapid adaptation of DNA restriction fragments. In addition, I have formulated a new model with regards to the mechanism of function for the 70 kDa family of heat shock proteins (hsp 70). This model proposes that hsp 70 serves as a cross-linker molecule between many cellular proteins and the cytoskeletal matrix, and this model may have significant implications on many cellular processes.
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Woo, Andrew Jonghan. "Characterization and identification of transcription factors that bind to the tumor necrosis factor -308 polymorphism." University of Western Australia. School of Biomedical and Chemical Sciences, 2003. http://theses.library.uwa.edu.au/adt-WU2004.0044.
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[Formulae and special characters can only be approximated. Please see the pdf version of this abstract for an accurate reproduction.] Tumor necrosis factor (TNF) is a pleiotropic cytokine that mediates a long list of immunological and pathophysiological processes. TNF is produced by a wide variety of cells including immune and non-immune cells, however in most cell types TNF is not expressed prior to stimulation. The function of TNF is mediated via its trimeric domain by binding to TNF receptors that are found on most types of cells, especially of the haematopoietic systems, hence transpiring its effects on a wide variety of cells and organ systems. The cytotoxic (apoptosis) and pro-inflammatory (differentiation, proliferation and activation) functions of TNF are protective but can also result in pathological or deleterious consequences. A biallelic G to A transition polymorphism in the promoter region of TNF at nucleotide position 308 from the transcription start site is suggested to be involved in differential transcriptional regulation of TNF expression. The high TNF producing 308A allele is associated with susceptibility to or worse outcome of many infectious diseases in addition to autoimmune and other pathophysiological conditions. A previous study in our laboratory observed a selective affinity towards the polymorphic 308A allele by an EMSA protein(s) complex, named E. Several other protein complexes were found along with complex E and one of them was identified as Sp1. The identification of complex E was unsuccessful but it was hypothesized to play a major role as transcriptional activator in 308A allele individuals hence transpiring its effect in various pathophysiological states. In this study, the EMSA complexes observed in the TNF promoter region between nucleotides 322 to 283, encompassing the 308 polymorphism, is characterized. EMSA using mutated oligonucleotides mapped the binding sites of complexes B, C, D and E. TRANSFAC database search in addition to previous work revealed the identity of complex C as Sp1 but the rest of complexes remained unknown. Moreover, in contrast to our previous study, the protein(s) in the complex E was found to preferentially bind 308G nucleotide hence posing as a transcriptional repressor, resulting in decreased production state of TNF in 308G allele individuals than 308A allele individuals. In order to characterize putative transcription factors binding to the promoter region, first the biochemical characteristics such as the effects of temperature, salts and cations on DNA binding ability of EMSA complexes were studied. EMSA complexes B, C, DI and E required cations, probably Zn+2, to bind DNA. By optimizing a technique that couples EMSA with SDS-PAGE, the molecular weight of C, DI and E was determined. A novel technique that couples EMSA with IEF determined the pI of complexes B, C, D, DI and E. Although a commonly used technique of identifying unknown DNA-binding protein of interest, Yeast One-Hybrid assay, did not identify complex E, the novel identification method involving chromatography, two-dimensional electrophoresis, EMSA, mass spectrometry and database interrogation successfully identified TNF EMSA complex E as transcription factor Ying Yang 1 (YY1). Supershift EMSA confirmed complex E as YY1. In addition, the supershift assay showed presence of Sp1 and Sp3 in complex C. Similarly, complex DI is identified as Sp3. The novel method in identifying DNA-binding proteins is particularly useful as this technique allows identification of protein seen in EMSA without the need of extensive identification process. YY1 binds to a 6 base pair sequence, 5? TTGAGG 3?, from nt 295 to 290 of TNF promoter. The loss of affinity in 308A allele is caused by transition of underlined G nucleotide to A. The determined and described molecular weight of YY1 in literature is 60 kDa while the theoretical weight is 45 kDa. Both the determined and theoretical pI of YY1 is 5.8. YY1 is a multifunctional transcription factor implicated in both positive and negative regulation of gene expression as well as in initiation of transcription. It is ubiquitously expressed in growing, differentiated, and growth-arrested cells. Although future experiment is yet to establish in vivo presence of YY1 in TNF promoter, our study so far provides convincing evidence that the putative transcription factor that has selective affinity towards 308G allele is indeed YY1.
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Heminger, Katherine Ann. "LOSS OF HDMX LEADS TO ALTERATIONS IN GENE EXPRESSION AND INHIBITION OF CELL GROWTH IN TUMOR CELLS WITH WILD-TYPE p53." Wright State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=wright1175282827.
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Shi, Shengli. "Effects of enhanced glutathione biosynthesis on oxidative stress-mediated hepatocellular injury and gene expression in mice /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/8470.
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Jansson, Agneta. "Molecular alterations in colorectal cancer /." Linköping : Univ, 2002. http://www.bibl.liu.se/liupubl/disp/disp2002/med743s.pdf.
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Rahman-Roblick, Rubaiyat. "The P53 pathway: role of telomerase and identification of novel targets : acts of a master regulator of tumor suppression /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-184-5/.
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Kelley, Kevin Daniel. "Understanding the Molecular Dynamics of YPEL3 and FHIT Gene Expression." Wright State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=wright1279328219.
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