Methylcobalamin decreases mRNA levels of androgen-induced growth factor inandrogen-dependent Shionogi carcinoma 115 cells

Methylcobalamin (MeCbl) is an important enzyme cofactor required for methio nine synthase activity. It also inhibits, in a dose-dependent manner, the p roliferation of an androgen-dependent cell line, SC-3, derived from an andr ogen-dependent mouse mammary tumor (Shionogi carcinoma 115). In SC-3 cells, androgen induces the production of androgen-induced growth factor (AIGF), an autocrine growth factor increasing the proliferation of SC-3 cells. MeCb l treatment suppressed the androgen-induced, AIGF-mediated growth of SC-3 c ells, as well as the androgen-induced increase of AIGF mRNA. In SC-3 cells, androgen receptors linked with androgen form complexes that tightly bind D NA and act as transcription factors in the nucleus to regulate the expressi on of specific genes such as AIGF. The number and dissociation constants of androgen receptors in control and MeCbl-treated SC-3 cells were the same. Similarly, the extent of binding of normal androgen receptors in nuclei fro m control and MeCbl-treated cells was virtually identical. The androgen rec eptors from control and MeCbl-treated cells showed similar capacities for c onversion to a form that tightly binds to DNA on heat activation. These res ults suggest that the reduction of AIGF mRNA, subsequent to the nuclear bin ding of androgen receptors, may be a partial cause of the growth-inhibitory activity of MeCbl in SC-3 cells.