Cellular-oncogene expression in Friend erythroleukemia cells: relationship to differentiation, commitment and TPA...

Induced differentiation of Friend erythroleukemia cells can be continuously and reversibly inhibited by phorbol ester tumor promoters, e.g. 12-O-tetradecanoylphorbol-13-acetate (TPA), for many years, allowing us to study the mechanisms of differentiation and its inhibition by TPA. We previously identified two steps in the differentiation process, which can be inhibited by TPA, before and after commitment to differentiation. Using permanently committed cells and TPA-resistant variants we examined the role of cellular oncogenes in Friend cell differentiation control, and their possible modulation by tumor-promoting phorbol esters. We report here characteristic changes in myc, myb and fos mRNA levels upon induction of differentiation by hexamethylene bisacetamide treatment, and present evidence that c-myb mRNA decline is one feature of Friend cell commitment to differentiation. In addition, using our TPA-sensitive and resistant cell lines, we observed that the hexamethylene bis-acetamide induced pattern of oncogene expression is unperturbed by TPA, regardless of whether the cells are differentiating or not.