Thyroid hormone inhibits androgen-enhanced DNA synthesis in Shionogi carcinoma 115 cells without affecting autocrine growth factor mRNA expression.
The growth of the mouse mammary Shionogi carcinoma 115 (SC 115)-derived cell line (SC-3) is markedly stimulated by androgen through induction of a heparin-binding growth factor termed androgen-induced growth factor (AIGF). This androgen-induced growth is partly blocked by thyroid hormone(s) such as triiodothyronine (T3). Transforming growth factor beta 1 (TGF beta 1) also inhibits the growth of SC-3 cells. Thus, we have investigated the possibility that T3 exerts its inhibitory effects on SC-3 cell growth through an alteration in AIGF or TGF beta 1 mRNA expression. Unexpectedly, T3 failed to modulate the expression of AIGF mRNA. T3 was also unable to significantly affect TGF beta 1 mRNA levels in androgen-stimulated SC-3 cells. More importantly, a neutralizing antibody against TGF beta 1 could not block T3-dependent inhibition of androgen-induced SC-3 cell growth. However, the inhibitory ability of T3 was potentiated by TGF beta 1. In addition, T3 treatment resulted in a significant inhibition of AIGF-induced DNA synthesis. Thus, T3 treatment renders SC-3 cells somehow refractory to AIGF. The signal pathway for T3 to reduce AIGF responsiveness may be shared by TGF beta 1.
Sumitani
S
S
Department of Medicine III, Osaka University Medical School, Japan.
Kasayama
S
S
Sato
B
B
D000818:Animals; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004357:Drug Synergism; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014284:Triiodothyronine / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; C496457:Fgf8 protein, mouse; D006133:Growth Substances; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016212:Transforming Growth Factor beta; D014284:Triiodothyronine; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors