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Oncogène RAS et Cancer Colorectal : Étude de la Réponse au Stress Oncogénique et de l'Échappement à la Sénescence

Abstract : Oncogene-Induced Senescence (OIS) is a tumor suppressor mechanism which prevent uncontrolled cells proliferation during oncogenic stress. During tumorigenesis, this process is inhibited by inactivation of tumor suppressor genes to allow proliferation and cell transformation. The OIS is described in primary cells, however, we have observed that this mechanism is conserved in transformed cells following the expression of H-RasV12. We investigated the regulation of this line of response in a colorectal adenoma cell line that have already inactivated tumor suppressors p16INK4a and p53. We observed that Ras oncogene induces p53-independent p21Waf1 expression which promotes senescence establishment. Under these conditions, we observed that p21Waf1 inhibits proliferation by transcriptional regulation of cell cycle genes Cdc25A and Plk1. In this work we noticed that some cells escaped to this arrest. By studying the presence of Senescence-Associated Heterochromatin Foci (SAHF), we observed that these cells loss senescence phenotype, and exhibit mesenchymal and dedifferentiation markers. These results suggests that upon expression of the oncogene Ras, some cells escape the OIS and this bypass exhaust is associated with an Epithelial-Mesenchymal Transition (EMT) and emergence of dedifferentiated cells. The bypass of Ras mediated OIS is associated to EMT and dedifferentiation. This mechanism might contribute to tumorigenesis.
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https://tel.archives-ouvertes.fr/tel-00588008
Contributor : Anne-Marie Plé <>
Submitted on : Friday, April 22, 2011 - 9:49:36 AM
Last modification on : Friday, October 23, 2020 - 4:38:17 PM
Long-term archiving on: : Thursday, November 8, 2012 - 5:11:31 PM

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  • HAL Id : tel-00588008, version 1

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Sophie de Carné Trécesson. Oncogène RAS et Cancer Colorectal : Étude de la Réponse au Stress Oncogénique et de l'Échappement à la Sénescence. Biologie cellulaire. Université d'Angers, 2010. Français. ⟨tel-00588008⟩

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