AN ESSENTIAL ROLE OF ANDROGEN-INDUCED GROWTH-FACTOR IN GLUCOCORTICOID-DEPENDENT AUTOCRINE LOOP IN SHIONOGI CARCINOMA-115 CELLS

Androgen-induced growth factor (AIGF) is essential for the androgen-induced autocrine growth of a mouse mammary Shionogi carcinoma cell line (SC-3 cells). Because glucocorticoid and estrogen have been observed to weakly stimulate DNA synthesis in SC-3 cells, the expression of AIGF mRNA after stimulation with various concentrations of androgen, glucocorticoid, or estrogen was examined by Northern blot analysis. Testosterone, dexamethasone, and estradiol-17 beta (E(2)) induced AIGF mRNA expression, although the maximum AIGF mRNA expression levels induced by dexamethasone or E(2) were lower than that by testosterone. Yet, diethylstilbestrol showed no induction, suggesting that the effect of E(2) could be mediated through the androgen receptor. The induction levels of AIGF mRNA by each steroid hormone were correlated positively with hormone-induced DNA synthesis. In addition, the DNA synthesis induced by each steroid hormone was almost completely inhibited by AIGF antisense oligonucleotides, indicating that AIGF is an obligatory component in not only the androgen- but also the glucocorticoid-inducible autocrine loop in SC-3 cells.