Gene Expression Profile Associated with Oncogenic Ras-induced Senescence, Cell Death, and Transforming Properties in Human Cells

Author： Moumtzi Sophy S.   Roberts Michael L.   Joyce Tobias   Evangelidou Maria   Probert Lesley   Frillingos Stathis   Fotsis Theodore   Pintzas Alexander  

Publisher： Informa Healthcare

ISSN： 0735-7907

Source： Cancer Investigation, Vol.28, Iss.6, 2010-06, pp. : 563-587

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Abstract

ABSTRACTWe developed inducible and constitutive expression systems of Ha-RasV12 in HEK 293 cells to examine early oncogenic RasV12 signaling. Inducible expression of oncogenic Ras-triggered growth arrest, early senescence, and later apoptosis. Gene expression profile analysis revealed early Ras proliferation and cell cycle genes like c-fos, cyclin E, cdk2, cell–cell contact, and signaling like integrin a6, MEK5, and free radical signaling genes, like proline oxidase. Therefore, Ras-mediated signaling is a fine regulated process both positively and negatively influencing cell cycle, senescence, and apoptosis pathways. Novel early RAS-target genes could be potentially exploited in cancer diagnostics and therapeutics.

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