Through gene-targeting, we have established human colon dancer 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-ras mediated signals and other immediate early genes, c-jun wag 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 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-Rat were same among these cells, however, the cytosolic PKC activity in HKe-3 was two times higher than that in HCT116 on serum-starved and serum-stimulated conditions. These results suggested that serum responsiveness of c-jun may be sup-pressed by activated Ki-ras through PKC rather than c-Raf pathway in colon cancer cells.
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