Alterations in c-myc expression in relation to maturational status of human colon carcinoma cells.

Previous work from this laboratory established a large bank of human colon carcinoma cell lines in culture and classified them with respect to growth regulatory phenotypes based on several biological and biochemical characteristics. In the present report, Northern analysis indicates that addition of the maturational agent N,N-dimethylformamide (DMF) (1.0%) to proliferating HCT 116 and MOSER cells resulted in a repression of c-myc proto-oncogene expression; retinoic acid (1.0 microM) was less effective in this regard. Repression of c-myc expression by DMF was observed in MOSER and HCT 116 cells, whether it was added to proliferating or late log phase cultures, and was associated with a corresponding reduction in cellular proliferation. The reduction in c-myc expression by DMF did not require new protein synthesis and occurred within a few minutes after its addition, resulting in a 70% reduction within approximately 2 hr. Previous work from this laboratory indicated that transforming growth factor-beta (TGF-beta) elicited alterations in MOSER cells similar to those observed following DMF treatment. The present report demonstrates that proliferating, but not late log phase, MOSER cells responded to TGF-beta with a repression of c-myc expression. Similarly, an inhibition of cellular proliferation was only observed when TGF-beta (10 ng/ml) was added to proliferating cells. Collectively, these findings indicate that repression of c-myc expression is associated with diminished cellular proliferation and the induction of a more benign phenotype in human colon carcinoma cells. Furthermore, this report is the first demonstration of a c-myc response to TGF-beta in an epithelial cell line.