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

ABSTRACT

We 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.

Keywords: :

• Ras
• Inducible
• Gene expression profile
• Cell death
• Proliferation
• Cancer

ACKNOWLEDGMENTS

This research was supported by European Union and GSRT grant numbers HPMD-CT-2001-00116, MTKD-CT-2004-509836, and 01ED113 (to A.P.).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.