CELL-DENSITY AND PARADOXICAL TRANSCRIPTIONAL PROPERTIES OF C-MYC AND MAX IN CULTURED MOUSE FIBROBLASTS

Deregulated expression of the c-Myc oncoprotein occurs in several huma n malignancies. The c-Myc protein behaves as a transcription factor, a nd undoubtedly its role in carcinogenesis involves its ability to affe ct the expression of genes involved in cell growth. c-Myc has been rep orted to both activate and repress transcription in transient transfec tion experiments using reporter constructs bearing multiple copies of the c-Myc binding site, CAC(G/A)TG. We investigated these apparently p aradoxical effects of c-Myc by determining if they arose from differen ces in the cell proliferation states of transfected cells. We found th at endogenous c-Myc protein levels vary inversely with the degree of c ell confluency, such that at low cell confluency, where endogenous lev els of c-Myc are high and presumably endogenous levels of Max are limi ting, exogenous c-Myc fails to affect basal transcription. In cells at high cell confluency, in which endogenous c-Myc levels are low, exoge nous c-Myc augments transactivation by titrating the relative excess e ndogenous Max. These observations suggest that the apparently paradoxi cal behavior of c-Myc in transfection experiments is partially depende nt on ambient cellular levels of c-Myc.