SUPPRESSION OF SERUM-INDUCED C-JUN EXPRESSION BY ACTIVATED KI-RAS IN HUMAN COLON-CANCER CELLS

Through gene-targeting, we have established human colon cancer cell li nes, HK2-6 and HKe-3, with and without activated Ki-ras, respectively, derived from a human colon cancer cell line HCT116, and we have repor ted that activated Ki-ras is involved in the deregulation of c-myc exp ression. To further examine the relation between Ki-ras-mediated signa ls and other immediate early genes, c-jun was analyzed on these cells stimulated by serum. Rapid and strong induction of c-jun was observed in HKe-3, but not in HCT116 or HK2-6. To elucidate the regulatory mech anisms of c-jun expression by Ki-ras, protein kinase C (PKC) and c-Raf were examined at serum-starved and serum-stimulated conditions. Phosp horylations of c-Raf were same among these cells, however, the cytosol ic PKC activity in HKe-3 was two times higher than that in HCT116 on s erum-starved and serum-stimulated conditions. These results suggested that serum responsiveness of c-jun may be suppressed by activated Ki-r as through PKC rather than c-Raf pathway in colon cancer cells.