Roles of Transforming Growth Factor 0 in Inhibition of Androgen-induced Growth of Shionogi Carcinoma Cells in Serum-free Medium1

Shionogi carcinoma 115 (SCI 15) has been accepted for 20 years as an androgen-responsive mouse mammary tumor. In a serum-free culture system we have established (Ham's F-l2:Eagle's minimum essential medium (1:1, v/v) containing 0.1% bovine serum albumin), 10 *M testos terone markedly stimulates the growth of SC-3 cells (a cloned cell line from a SCI 15 tumor) via androgen receptor. The testosterone-induced growth of SC-3 cells, which has been shown to be mediated through autocrine fibroblast growth factor (FGF)-like peptide, was almost com pletely abolished by 1 ng/ml of transforming growth factor ß(TGF-/J). In the present study, mechanisms of the inhibitory effect of TGF-/J on the testosterone-induced growth of SC-3 cells were examined in the serum-free medium. Although the testosterone-induced growth was al most completely inhibited by TGF-0, basic FGFor FGF-like peptide (secreted from SC-3 cells by testosterone)-induced growth was only partially inhibited (45%) by TGF-0. This difference can be explained by the fact that TGF-/3 decreased the amount of testosterone-induced FGFlike peptide secreted from SC-3 cells to 18% of control. The TGF-/9induced inhibition was found to be reversible. Furthermore, no significant effects of the K.I-,) treatment on number or affinity of both androgen and FGF receptors were demonstrated. The present findings show that TGF-/? markedly inhibits testosterone-induced secretion of FGF-like peptide from SC-3 cells and also inhibits growth-stimulatory effects of the secreted factor on SC-3 cells, probably via postreceptor mechanisms.