Roles of transforming growth factor beta in inhibition of androgen-induced growth of Shionogi carcinoma cells in serum-free medium.
Shionogi carcinoma 115 (SC115) 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-12:Eagle's minimum essential medium (1:1, v/v) containing 0.1% bovine serum albumin], 10(-8) M testosterone markedly stimulates the growth of SC-3 cells (a cloned cell line from a SC115 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 completely abolished by 1 ng/ml of transforming growth factor beta (TGF-beta). In the present study, mechanisms of the inhibitory effect of TGF-beta on the testosterone-induced growth of SC-3 cells were examined in the serum-free medium. Although the testosterone-induced growth was almost completely inhibited by TGF-beta, basic FGF- or FGF-like peptide (secreted from SC-3 cells by testosterone)-induced growth was only partially inhibited (45%) by TGF-beta. This difference can be explained by the fact that TGF-beta decreased the amount of testosterone-induced FGF-like peptide secreted from SC-3 cells to 18% of control. The TGF-beta-induced inhibition was found to be reversible. Furthermore, no significant effects of the TGF-beta treatment on number or affinity of both androgen and FGF receptors were demonstrated. The present findings show that TGF-beta 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.
Yamanishi
H
H
Department of Pathology, Osaka University Medical School, Japan.
Nonomura
N
N
Tanaka
A
A
Yasui
T
T
Nishizawa
Y
Y
Matsumoto
K
K
Sato
B
B
D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D004273:DNA, Neoplasm / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D006133:Growth Substances / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D011944:Receptors, Androgen / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor; D013739:Testosterone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003470:Culture Media; D004273:DNA, Neoplasm; D006133:Growth Substances; D011944:Receptors, Androgen; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D013739:Testosterone; D005346:Fibroblast Growth Factors; D015291:Transforming Growth Factors; D006493:Heparin