Crucial role of c-myc in 1,25(OH)2D3 control of C-cell-carcinoma proliferation

1,25(OH)2D3 (1,25D3) enhances DNA synthesis and cell proliferation in the human C-cell carcinoma cell line (TT). These effects are dependent on previous stimulation of c-myc gene expression. Since the TT cell line has lost some characteristic C-cell features, we investigated the rat rMTC 6-23 line to assess whether the 1,25D3 effects on TT cells are representative of C-cell carcinoma cells. Addition of 1,25D3 (10(-7)M) led to a 2.5-fold stimulation of 3H-thymidine incorporation (3H-T) in TT cells, which was preceded by a 2-fold increase in c-myc mRNA. In contrast, in proliferating nonstimulated rMTC 6-23 cells, c-myc mRNA was undetectable. Upon addition of 1,25D3 to these cells, 3-HT decreased to 70% of control, with no change in c-myc expression. Thus, the stimulatory effect of 1,25D3 in TT cells seems to depend, at least in part, on a c-myc-dependent pathway.