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Academic literature on the topic 'Cellular immortalisation'
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Journal articles on the topic "Cellular immortalisation"
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Argyle, D., V. Ellsmore, E. A. Gault, A. F. Munro, and L. Nasir. "Equine telomeres and telomerase in cellular immortalisation and ageing." Mechanisms of Ageing and Development 124, no. 6 (June 2003): 759–64. http://dx.doi.org/10.1016/s0047-6374(03)00104-0.
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Thiers, B. H. "Cellular senescence in naevi and immortalisation in melanoma: a role for p16?" Yearbook of Dermatology and Dermatologic Surgery 2007 (January 2007): 340–41. http://dx.doi.org/10.1016/s0093-3619(08)70622-1.
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Gray-Schopfer, V. C., S. C. Cheong, H. Chong, J. Chow, T. Moss, Z. A. Abdel-Malek, R. Marais, D. Wynford-Thomas, and D. C. Bennett. "Cellular senescence in naevi and immortalisation in melanoma: a role for p16?" British Journal of Cancer 95, no. 4 (August 2006): 496–505. http://dx.doi.org/10.1038/sj.bjc.6603283.
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Sonigra, Rakesh J., Shivanthi S. Kandiah, and Caroline B. Wigley. "Spontaneous immortalisation of ensheathing cells from adult rat olfactory nerve." Glia 16, no. 3 (March 1996): 247–56. http://dx.doi.org/10.1002/(sici)1098-1136(199603)16:3<247::aid-glia7>3.0.co;2-z.
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Kerr, Jonathan R. "Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors." Journal of Clinical Pathology 72, no. 10 (July 17, 2019): 651–58. http://dx.doi.org/10.1136/jclinpath-2019-205822.
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Epstein-Barr virus (EBV) is a ubiquitous human virus which infects almost all humans during their lifetime and following the acute phase, persists for the remainder of the life of the individual. EBV infects B lymphocytes leading to their immortalisation, with persistence of the EBV genome as an episome. In the latent phase, EBV is prevented from reactivating through efficient cytotoxic cellular immunity. EBV reactivates (lytic phase) under conditions of psychological stress with consequent weakening of cellular immunity, and EBV reactivation has been shown to occur in a subset of individuals with each of a variety of cancers, autoimmune diseases, the autoimmune-like disease, chronic fatigue syndrome/myalgic encephalitis and under other circumstances such as being an inpatient in an intensive care unit. Chronic EBV reactivation is an important mechanism in the pathogenesis of many such diseases, yet is rarely tested for in immunocompetent individuals. This review summarises the pathogenesis of EBV infection, EBV reactivation and its role in disease, and methods which may be used to detect it. Known inhibitors of EBV reactivation and replication are discussed, including drugs licensed for treatment of other herpesviruses, licensed or experimental drugs for various other indications, compounds at an early stage of drug development and nutritional constituents such as vitamins and dietary supplements.
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Toussaint, Olivier, Patrick Dumont, Jose Remacle, Jean-Francois Dierick, Thierry Pascal, Christophe Frippiat, Joao Pedro Magalhaes, Stephanie Zdanov, and Florence Chainiaux. "Stress-Induced Premature Senescence or Stress-Induced Senescence-Like Phenotype: OneIn VivoReality, Two Possible Definitions?" Scientific World JOURNAL 2 (2002): 230–47. http://dx.doi.org/10.1100/tsw.2002.100.
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No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1). Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2). As stress increases, the proportion of cells in “stress-induced premature senescence-like phenotype” according to definition 1 or “stress-induced premature senescence,” according to definition 2, should increase when a culture reaches growth arrest, and the proportion of cells that reached telomere-dependent replicative senescence due to the end-replication problem should decrease. Stress-induced premature senescence-like phenotype and telomere-dependent replicatively senescent cells share basic similarities such as irreversible growth arrest and resistance to apoptosis, which may appear through different pathways. Irreversible growth arrest after exposure to oxidative stress and generation of DNA damage could be as efficient in avoiding immortalisation as “telomere-dependent” replicative senescence. Probabilities are higher that the senescent cells (according to definition 2) appearingin vivoare in stress-induced premature senescence rather than in telomere-dependent replicative senescence. Examples are given suggesting these cells affectin vivotissue (patho)physiology and aging.
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Norton, J. D. "ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis." Journal of Cell Science 113, no. 22 (November 15, 2000): 3897–905. http://dx.doi.org/10.1242/jcs.113.22.3897.
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The ubiquitously expressed family of ID helix-loop-helix (HLH) proteins function as dominant negative regulators of basic HLH (bHLH) transcriptional regulators that drive cell lineage commitment and differentiation in metazoa. Recent data from cell line and in vivo studies have implicated the functions of ID proteins in other cellular processes besides negative regulation of cell differentiation. ID proteins play key roles in the regulation of lineage commitment, cell fate decisions and in the timing of differentiation during neurogenesis, lymphopoiesis and neovascularisation (angiogenesis). They are essential for embryogenesis and for cell cycle progression, and they function as positive regulators of cell proliferation. ID proteins also possess pro-apoptotic properties in a variety of cell types and function as cooperating or dominant oncoproteins in immortalisation of rodent and human cells and in tumour induction in Id-transgenic mice. In several human tumour types, the expression of ID proteins is deregulated, and loss- and gain-of-function studies implicate ID functions in the regulation of tumour growth, vascularisation, invasiveness and metastasis. More recent biochemical studies have also revealed an emerging ‘molecular promiscuity’ of mammalian ID proteins: they directly interact with and modulate the activities of several other families of transcriptional regulator, besides bHLH proteins.
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Arlett, Colin F., Michael H. L. Green, Anne Priestley, Susan A. Harcourt, and Lynne V. Mayne. "Comparative Human Cellular Radiosensitivity: I. The Effect of SV40 Transformation and Immortalisation on the Gamma-irradiation Survival of Skin Derived Fibroblasts from Normal Individuals and from Ataxia-telangiectasia Patients and Heterozygotes." International Journal of Radiation Biology 54, no. 6 (January 1988): 911–28. http://dx.doi.org/10.1080/09553008814552321.
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Evrard, C., M. Le Bert, I. Borde, P. Rouget, E. Galiana, and R. Bemard. "Transfert de gènes dans les cellules nerveuses: immortalisation cellulaire et marquage génétique." médecine/sciences 7, no. 4 (1991): IX. http://dx.doi.org/10.4267/10608/4373.
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Giotopoulos, George, Wai-In Chan, David Ruau, Paolo Gallipoli, Alexis Fowler, Berthold Göttgens, Jan Van Deursen, Philip Cole, and Brian Huntly. "The Epigenetic Regulators CBP and p300 Facilitate Leukemogenesis and Represent Therapeutic Targets In Acute Myeloid Leukemia (AML)." Blood 122, no. 21 (November 15, 2013): 3732. http://dx.doi.org/10.1182/blood.v122.21.3732.3732.
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Abstract Although molecularly and clinically heterogeneous, AML is characterised by aberrant transcription and abnormal epigenetic regulation. The transcriptional co-activators CBP and p300 have well characterised roles in hematopoiesis and hematopoietic stem cell (HSC) function. These are mutated in AML and also bind a number of AML-associated oncogenes. However, despite this, their roles in the induction and maintenance of AML are poorly understood. To address this question, we have combined genetic and pharmacological inhibition of CBP and p300 in AML and normal hematopoiesis. Using a murine model where Cbp was conditionally deleted from murine hematopoietic stem and progenitor cells (HSPC), either prior to, or following expression of a number of AML-associated oncogenes, we assessed the role of Cbp in the induction and maintenance of AML. We demonstrated that although not an absolute requirement, Cbp confers a selective advantage for robust immortalisation in vitro, and that Cbp is also an important requirement for the generation and maintenance of AML in vivo. Furthermore, redundancy between Cbp and p300 in myeloid transformation was demonstrated, as p300 knockdown further decreased proliferation in Cbp-/- AML cells. We next validated CBP/p300 as potential therapeutic targets, using a pharmacological strategy. Using a selective small molecule inhibitor (C646) of the lysine acteyltranferase (KAT) activity of CBP/p300, we demonstrated a significant decrease in growth and clonogenic potential across multiple AML subtypes in vitro. This was mediated through induction of apoptosis and cell cycle arrest. Importantly, no alteration in the growth of normal murine and human hematopoietic progenitors was detected at similar doses. We further demonstrated that inhibition of CBP/p300 KAT activity in human leukemia cells alters a transcriptional programme associated with genomic integrity, linking transcriptional changes to the cellular phenotype. Finally, we demonstrated the efficacy of the HAT inhibitors to decrease clonogenic growth across a panel of primary AML patient samples, representing multiple genetic subtypes. Taken together, these data suggest that CBP/p300 are involved in leukemogenesis across multiple subtypes in AML and that targeting these proteins may be possible with an acceptable side-effect profile. Disclosures: No relevant conflicts of interest to declare.
Dissertations / Theses on the topic "Cellular immortalisation"
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Kan, Chin-Yi. "Human Papillomavirus in human breast cancer and cellular immortalisation." Sydney : University of New South Wales. Biotechnology and Biomolecular Sciences, 2007. http://www.library.unsw.edu.au/~thesis/adt-NUN/public/adt-NUN20071004.080541/.
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Linne, Hannah Louise. "Investigating telomerase regulation in human breast cancer cells : a search for telomerase repressor sequences localised to chromosome 3P." Thesis, Brunel University, 2015. http://bura.brunel.ac.uk/handle/2438/11620.
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Cellular immortality is one of the ten hallmarks of human cancer and has been shown to be an essential prerequisite for malignant progression (Hanahan and Weinberg., 2011, Newbold et al., 1982, Newbold and Overell., 1983). In contrast, normal human somatic cells proliferate for a limited number of population doublings before entering permanent growth arrest known as replicative senescence. This is thought to be due to the progressive shortening of telomeric sequences with each round of cell division. Over 90% of human tumours, but not the majority of human somatic cells, have been found to express telomerase activity (Kim et al., 1994). The rate-limiting component of the human telomerase enzyme is the telomerase reverse transcriptase subunit, which is encoded by the hTERT gene. Transfection of hTERT cDNA into normal human fibroblasts and epithelial cells may sometimes be sufficient to confer cellular immortality (Newbold., 2005, Stampfer and Yaswen., 2002). Therefore, de-repression of hTERT and telomerase re-activation are thought to be critical events in human carcinogenesis and is the predominant mechanism by which cancer cells maintain their proliferative capacity. Previously, our group has shown that introduction of a normal, intact copy of human chromosome 3 into the 21NT primary breast cancer cell line by microcell-mediated monochromosome transfer (MMCT), is associated with strong telomerase repression and induction of cell growth arrest within the majority of hybrid clones (Cuthbert et al., 1999). Structural mapping of chromosome 3 within telomerase-positive revertent clones revealed two regions of deletion: 3p21.3-p22 and 3p12-p21.1, thought to harbour the putative telomerase repressor sequence(s). Subsequent studies showed that the chromosome 3p-encoded telomerase repressor sequence(s) mediates its function by means of transcriptional silencing of hTERT, in part, through chromatin remodelling of two sites within intron 2 of the hTERT gene (Ducrest et al., 2001, Szutorisz et al., 2003). Attempts to achieve positional cloning of hTERT repressor sequences on chromosome 3p identified two interesting candidates; the histone methyltransferase SETD2 and an adjacent long non-coding RNA (lncRNA) sequence known as FLJ/KIF9-AS1 (Dr. T. Roberts, unpublished data). Through MMCT-mediated introduction of intact chromosomes 3 and 17 into the 21NT cell line, I have demonstrated that at least two as yet unidentified telomerase repressor sequences (one located on each of these two normal chromosomes) may function to repress telomerase activity within the same breast cancer cell line, which suggests that multiple, independent telomerase regulatory pathways may be inactivated within the same cancer type. Furthermore, by examining the consequences of forced SETD2 and FLJ expression within the 21NT cell line, together with siRNA-mediated knockdown of SETD2 within a single telomerase-repressed 21NT-chromosome 3 hybrid, I have provided evidence to show that neither of these two candidate genes may function as a regulator of hTERT transcription. Through interrogation of relevant literature, a set of four candidate 3 telomerase regulatory genes (BAP1, RASSF1A, PBRM1 and PARP-3) were selected for further investigation based on their location within the 3p21.1-p21.3 region together with their documented role in the epigenetic regulation of target gene expression. Using mammalian expression vectors containing candidate gene cDNA sequences, my colleague Dr. T. Roberts and I demonstrated that forced overexpression of BAP1 and PARP-3 within the 21NT cell line is associated with consistent, but not always sustained, repression of hTERT transcriptional activity and telomerase activity. It is therefore possible that at least two sequences may exist on chromosome 3p that function collectively to regulate hTERT expression within breast cancer cells. Finally, using an in vitro model of human mammary epithelial cell (HMEC) immortalization, involving the targeted abrogation of two pathologically relevant genes, p16 and p53 to generate a series of variant clones at different stages of immortal transformation (developed by my colleague Dr. H. Yasaei), I have shown that single copy deletions on chromosome 3p are a frequent, clonal event, specifically associated with hTERT de-repression and immortal transformation. Subsequent high-density single nucleotide polymorphism (SNP) array analysis of immortal variants carried out by Dr. H. Yasaei, identified a minimal common region of deletion localized to 3p14.2-p22. Together, these findings provide additional evidence to show that chromosome 3p may harbour critical hTERT repressor sequences, that are lost as an early event during breast carcinogenesis.
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Parouchev, Alexandre. "Immortalisation et transplantation de cellules hépatiques simiennes : modèles de thérapie cellulaire hépatique." Paris 7, 2010. http://www.theses.fr/2010PA077099.
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La transplantation orthotopique de foie est le seul traitement curatif de certains déficits métaboliques. Mais, le manque de donneurs et les complications liées à l’ immunosuppression incitent au développement d'alternatives thérapeutiques, dont la transplantation d'hépatocytes. Cependant, à ce jour les essais avec hépatocytes adultes sont peu fructueux. Nous avons exploré deux voies thérapeutiques. D'une part dans la recherche de sources alternatives de cellules, nous avons caractérisé une lignée de cellules hépatiques fœtales simiennes (IPFLS), immortalisées par l'antigène T de SV40, à long terme. In vitro ces cellules conservent leur capacité de prolifération et leur phénotype de progéniteurs hépatiques bipotents. Leur immortalisation est réversible après excision de Foncogène par Cre. In vivoy elles sont non tumorigènes et se différencient en hépatocytes, sans proliférer in situ. Toutefois, leur importante instabilité du caryotype souligne la nécessité d'évaluer d'autres gènes d'immortalisation. D'autre part, la thérapie génique ex vivo est une alternative à l’allotransplantation d'hépatocytes. Nous avons mis au point la transduction d'hépatocytes simiens adultes, fraîchement isolés et cryopréservés, en suspension par des lentivirus recombinants dérivés de VTH-1, exprimant GFP sous contrôle du promoteur hépatospécifique du gène de l’apolipoprotéine A-II humain. La fonctionnalité in vivo, des hépatocytes cryopréservés est attestée par la présence d'hépatocytes transduits trois mois après transplantation dans le foie de souris immunodéficientes. Le modèle du primate non humain est un bon modèle préclinique pour des approches de thérapie génique ex vivo à visée hépatiqueOrthotopic liver transplantation is the only available cure for certain metabolic deficiencies. But, lack of donors and complications related to immunosuppression urge the development of alternatives therapies such as hepatocyte transplantation. However, trials with adult hepatocytes have been so far disappointing. We have explored two directions. As a model for an alternative source of hépatocytes, we have characterized a line of simian fetal hepatic cells (IPFLS), immortalized by SV40-T antigen. In vitro these cells conserve their proliferative capacity and their hepatic bipotent progenitor phenotype. The immortalization is reversible after Cre-mediated excision of the oncogene. In vivo, they are non tumorigenic and differentiate into hepatocytes, with no in situ proliferation. However, the important karyotype instability underlines the need for new immortali2ation strategies. Moreover, ex vivo gene therapy is considered as an alternative to hepatocyte allotransplantation. We have set up conditions for efficient transduction of freshly-isolated and cryopreserved, adult, simian hepatocytes in suspension by HIV-1-derived recombinant lentiviruses, expressing GFP under transcriptional control of the hepatospecific promoter of the human apolipoprotein A-II gene. The in vivo persistence and fonction of cryopreserved cells is demonstrated by the presence of transduced hepatocytes three months after transplantation into the liver of immunodeficient mice. Thus the nonhuman primate appears as a good preclinical model for the development of liver-directed ex vivo gene therapy strategies
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Bernard, Rozenn. "Transfert de gènes dans des précurseurs gliaux : immortalisation cellulaire, prolifération et différenciation des lignées établies." Paris 11, 1994. http://www.theses.fr/1994PA11T009.
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Allain, Jean-Etienne. "Immortalisation et transplantation de cellules foetales hépatiques simiennes et humaines : modèles de thérapie cellulaire hépatique." Paris 7, 2002. http://www.theses.fr/2002PA077004.
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Bayad, Jamal. "Immortalisation de lignées cellulaires hépatocytaires : expression et régulation des enzymes du métabolisme des xenobiotiques." Nancy 1, 1991. http://www.theses.fr/1991NAN10450.
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Delgado, Charris Jean-Paul. "Caractérisation phénotypique et moléculaire des cellules progénitrices foetales hépatiques simiennes et humaines." Paris 11, 2006. http://www.theses.fr/2006PA114825.
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Le foie est un organe de cible pour les thérapies cellulaires. Les perspectives de ces approches avec les hépatocytes humains adultes sont limitées : manque de données, absence de prolifération, et inefficacité de greffe. Nous avons caractérisé phénotypiquement à différents doublements de population (DP) une lignée d’hépatoblastes bipotents de singe immortalisés (IPFLS) dans le laboratoire à l’aide de l’oncogène T de SV40 flanqué de sites LoxP. Nous avons montré que l’immortalisation était réversible après excision du transgène par transduction rétrovirale du gène codant la Cre recombinase. Nous avons aussi montré qu’aux passages tardifs (120DP) l’activité télomérase était réduite, les télomères raccourcis et les remaniements chromosomiques importants. Après transplantation dans des souris immunodéficientes, les cellules IPFLS se sont différenciées en hépatocytes mais n’ont pas proliféré. Nous avons contribué à l’isolement et la caractérisation des hépatoblastes/hépatocytes fœtaux humains précoces (10-12 semaines). Après transplantation, ces cellules repeuplent plus efficacement le foie des souris transplantées que les IPFLS. In vitro elles ont un potentiel de migration et d’invasion, au contraire des hépatocytes adultes, qui est accru après stimulation par HGF. Ce processus est corrélé à une augmentation de la sécrétion et l’activation des métalloprotéases 2 et 9 et à une activation de la voie ERK. La transplantation d’hépatoblases stimulés par HGF dans des souris nouveau-nées améliore la dispersion de ces cellules dans le parenchyme hépatique. Ces résultats suggèrent que les hépatoblastes humains ont des propriétés spécifiques qui permettront d’améliorer la prise de greffeThe liver is a target organ for cell-based therapies. The use of human adult hepatocytes for such approaches is limited by the lack of donors, the absence of proliferation and low cell engraftment. We characterized a simian bipotent hepatoblast line (IPFLS) immortalized in our lab by using the Sv40 virus T oncogene flanked by LoxP sites, at different population doublings (PD). We showed that immortalization process was reversible after Cre recombinase mediated retroviral gene transfer. We also showed a telomerase activity reduction correlated with telomere shortening and chromosomal rearrangements at 120 PD. After transplantation in the liver of immunocompromised mice, IPFLS cells were differentiated into hepatocytes but did not proliferate. We contributed to the isolation and characterization of early fetal human heptoblasts/hepatocytes (10-12 weeks). After transplantation, these cells repopulated more efficiently the liver of transplanted mice than IPFLS cells. Human hepatoblasts, contrary tu adult hepatocytes, have an in vitro migration and invasion potential which is enhanced by the Hepatocyte Growth Factor (HGF). This process is correlated with an up regulation in the secretion and activation of matrix metalloproteinases 2 and 9 and the activation of the ERK pathway. Transplantation of hepatoblasts stimulated with HGF into new born mice improves cell spreading in the liver parenchyma. These results suggest that human hepatoblasts have specific properties which allow the improvement of cell engraftement
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Aure, Karine. "Physiopathologie moléculaire et cellulaire des maladies mitochondriales à présentation neurologique." Paris 6, 2007. http://www.theses.fr/2007PA066281.
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Les maladies mitochondriales sont liées à un déficit de la chaîne respiratoire mitochondriale. Ces maladies posent des problèmes de diagnostic, dans leurs relations phénotype/génotype et dans leurs mécanismes physiopathologiques. L'étude longitudinale d'un cas de déficit en ubiquinone a démontré les limites de la supplémentation thérapeutique. L'analyse de l’histoire naturelle et des caractéristiques moléculaires de 69 patients porteurs de délétion de l’ADN mitochondrial a permis d'établir une nouvelle classification clinique et des facteurs pronostiques. L’efficacité de l’immortalisation par le gène de la télomérase a été démontrée dans les fibroblastes déficitaires. Nous avons montré la présence d’apoptose dans le muscle de patients avec mutations de l'ADN mitochondrial. Les difficultés de la démonstration du pouvoir délétère des mutations homoplasmiques de l’ADN mitochondrial ont été abordées à travers l'étude de familles portant la même mutation de l'ARN de transfert de la proline.
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DJELLOUL, SIHAM. "Immortalisation des cellules epitheliales digestives par l'oncogene grand t de sv40 : consequences sur la transformation, la differenciation et l'effet antiproliferatif du tgf1." Paris 6, 1997. http://www.theses.fr/1997PA066066.
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Nous demontrons ici que l'immortalisation de cellules epitheliales isolees de l'estomac ou de l'intestin chez le rat (modeles rgc et eski), apres infection par des retrovirus recombinants pour le sv40lt, est associee a l'emergence de cellules epitheliales 1) relativement indifferenciees et possedant certains determinants specifiques de l'epithelium digestif 2) capables de resister aux effets antiproliferatifs du tgf. Cependant, la differenciation enterocytaire est compatible avec le transfert de sv40lt et la perte de l'anti-oncogene p53 dans les cellules coliques humaines caco-2, suggerant ainsi que cet oncogene viral a un effet permissif quand il est introduit dans des cellules epitheliales digestives deja differenciees et un effet represseur de la differenciation quand il est introduit dans un compartiment de cellules normales, germinatives et indifferenciees. Le phenotype dominant de la differenciation enterocytaire dans les cellules caco-2 peut egalement s'expliquer par surexpression des anti-oncoproteines prb1 et prb2 qui forment des complexes moleculaires avec l'antigene sv40lt, et l'independance de ces cellules aux facteurs de croissance exogenes. La perte des effets antiproliferatifs du tgf engendres par le sv40lt et l'immortalisation cellulaire peut s'expliquer en partie par la reduction selective du nombre de recepteurs du tgf de type i, mais n'implique pas la perte de leur fonctionalite. Les recepteurs du tgf (types i et ii) retiennent la capacite d'activer : 1) la serine/threonine kinase p78, impliquee dans les effets antiproliferatifs du tgf, 2) les gtpases de la famille rho et la voie de jnk qui sont des elements intermediaires dans la transmission du signal transcriptionnel du tgf et de l'apoptose. Le sv40lt interfere avec la signalisation du tgf au niveau de l'element de reponse de l'inhibiteur de l'activateur du plasminogene pai-1 qui intervient dans les processus de remodelage de la matrice extracellulaire et l'invasion. L'ensemble de ces travaux ouvre de nouvelles perspectives sur l'elucidation et le controle des mecanismes impliques dans l'independance des tumeurs humaines aux facteurs de croissance et dans leur resistance aux effets antiproliferatifs du tgf.
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BORDE, ISABELLE. "Transfert de genes et immortalisation de precurseurs de cellules nerveuses murines. Etude de la proliferation et de la differenciation des lignees immortalisees." Paris 7, 1994. http://www.theses.fr/1994PA077012.
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Nous avons transferre de facon stable, dans des cellules nerveuses murines, des genes immortalisants: les oncogenes grand t de polyome et grand t de sv40. Nous avons ainsi obtenu des lignees cellulaires variees issues de differentes regions du cerveau (cortex, mesencephale et striatum) qui correspondent a differents types de precurseurs de cellules nerveuses. D'autres lignees ont ete etabli a partir de souris transgeniques portant le gene grand t du virus polyome. Certaines de ces lignees sont des precurseurs astrogliaux qui montrent une correlation entre le controle de la division cellulaire et leur differenciation terminale. Des lignees etablies apres transduction retrovirale du grand t de sv40, presentent des caracteristiques de precurseurs astrocyte-neurone, et expriment un ensemble de recepteurs de type adrenergique, dopaminergique, muscarinique et serotoninergique, caracteristique de cette region du cerveau. Nous avons precise les differentes sous-classes de recepteurs dopaminergiques exprimees par ces cellules. Des vecteurs retroviraux recombinants dans lesquels l'oncogene immortalisant grand t de polyome est place entre les ltr du genome d'un retrovirus neurogliotrope le cas-br-e mulv, nous ont permis d'etablir plusieurs lignees de cellules nerveuses, dont certaines expriment des marqueurs de differenciation de cellules gliales. Un clone immortalise apres transfection des sequences e1a, qui est un precurseur bipotent oligodendrocyte-astrocyte, peut entrer en apoptose dans certaines conditions de culture restrictives. Ces lignees sont appropriees a des etudes pharmacologiques. Elles presentent egalement un interet particulier pour des etudes concernant l'effet des facteurs de croissance sur la division, la differenciation et l'apoptose ainsi que pour analyser des genes impliques dans ces processus