RAF-1 KINASE, EPIDERMAL GROWTH-FACTOR RECEPTORS, AND MUTANT RAS PROTEINS IN COLONIC CARCINOMAS

Epidermal growth factor receptors (EGFR) and ms mutations are known to play a significant role in controlling cell growth and tumor promotio n. Both of them transmit mitogenic signals to the nucleus by activatio n of Raf-1 kinase. In this study, the expression of EGFR and mutant Ra s proteins, and, for the first time, the expression, phosphorylation a nd kinase activity of Raf-1 kinase have been determined in paired samp les of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activ ity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), b ut only 1/20 of the cancer samples, contained hyperphosphorylated Raf- 1. EGFR were significantly (p = 0.0025) decreased in the tumors. The d ecreased phosphorylation of Raf-1 in colonic carcinomas could be the r esult of activation of Raf-1 phosphatases or inactivation of kinases p hosphorylating Raf-1. New forms of treatment based on EGFR overexpress ion do not seem to be suitable for the majority of colonic cancers.