Effect of differentiation agents on C-MYC expression in transformed fibroblasts and in human colon carcinoma cells

Previous work in this laboratory indicated that growth of methylcholanthrene-transformed AKR-2B fibroblasts (AKR-MCA), as well as certain human colon carcinoma lines on retinoic acid (RA) or N,N-dimethylformamide (DMF) resulted in a more differentiated phenotype. Moreover, morphological transformation of AKR-2B cells by transforming growth factor-..beta.. was blocked by simultaneous addition of DMF. In the present work Northern transfer analysis of total cellular RNA was utilized to determine the effect of these differentiation agents (DA) on c-myc expression. Expression of the c-myc proto-oncogene was elevated 2 to 4 fold in AKR-MCA cells relative to untransformed AKR-2B cells. 1.0% DMF resulted in a decrease in c-myc expression in AKR-MCA cells to a level at or below that in AKR-MCA cells. RA treatment (1.0 ..mu..M) of AKR-MCA cells reduced c-myc expression to a level intermediate between AKR-MCA and AKR-2B cells. Similarly, growth of human colon carcinoma cells (HCT 116 and MOSER) on 0.5% DMF or 1.0 ..mu..M RA resulted in a greater reduction of c-myc expression by DMF than by RA. These DA's may act by inhibition of oncogene-mediated cell responsiveness to positive autocrine growth factors, or alternatively, by stimulation of oncogene-mediated responsiveness to growth inhibitory factors.