Suppression of serum-induced c-jun expression by activated Ki-ras in human colon cancer cells

Abstract

SummaryThrough gene-targeting, we have established human colon cancer cell lines, HK2-6 and HKe-3, with and without activated Ki-ras, respectively, derived from a human colon cancer cell line HCT116, and we have reported that activated Ki-ras is involved in the deregulation of c-myc expression. To further examine the relation between Ki-rasmediated signals and other immediate early genes, c-jun was analyzed on these cells stimulated by serum. Rapid and strong induction ofc-jun was observed in HKe-3, but not in HCTII6 or HK2-6. To elucidate the regulatory mechanisms of c-jun expression by Ki-ras, protein kinase C (PKC) and c-Raf were examined at serum-starved and serum-stimulated conditions. Phosphorylations of c-Raf were same among these ceils, however, the cytosolic PKC activity in HKe-3 was two times higher than that in HCTI16 on serum-starved and serum-stimulated conditions. These results suggested that serum responsiveness of c-jun may be suppressed by activated Ki-ras through PKC rather than c-Raf pathway in colon cancer cells.