Analysis of c-raf oncogene expression in gastrointestinal tumor cells.

Abstract

Oncogenes of retroviruses are responsible for the induction of tumors in animals and for the malignant transformation of cells in culture. They are derived from normal cellular proto-oncogenes. Comparison of differences between viral oncogenes and proto-oncogenes has indicated that they are never identical. In human tumors that are not induced by retroviruses, activated proto-oncogenes have been discovered which resemble the viral oncogenes in properties such as mutations, deletions, or amplified expression [1]. Activated oncogenes have been described in many different tumors or tumor cell lines [2]. Often, more than one oncogene seems to be activated, e.g., in HL60 promyelocyte leukemic cells myc, myb and mil/raf are amplified ([3] and unpublished observation). We are interested in the expression of the activated proto-oncogene c-mil/raf in human tumors. It is the homologue to the oncogene v-mil of the avian retrovirus MH2[4] While v-mil is expressed in virus- transformed cells as pl00gag-mil fusion protein, the cellular homologue exhibits a molecular weight of 74 kD, p74hu-c-raf [5] The v-mil protein is located predominantly in the cytoplasm and exhibits a virus-coded protein kinase activity in autophosphorylation reactions specific for the amino acids serine and threonine [6, 7]. It renders the cells independent of growth factors and therefore is involved in alteration of the signal transduction characteristic of many tumor cells.