Sumitani S, Kasayama S, Sato B
Department of Medicine III, Osaka University Medical School, Japan.
J Steroid Biochem Mol Biol. 1994 Jul;50(1-2):5-11. doi: 10.1016/0960-0760(94)90166-x.
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.
源自小鼠乳腺癌Shionogi 115（SC 115）的细胞系（SC - 3）的生长受到雄激素的显著刺激，雄激素通过诱导一种名为雄激素诱导生长因子（AIGF）的肝素结合生长因子来实现。这种雄激素诱导的生长部分受到甲状腺激素如三碘甲状腺原氨酸（T3）的阻断。转化生长因子β1（TGFβ1）也抑制SC - 3细胞的生长。因此，我们研究了T3是否通过改变AIGF或TGFβ1 mRNA表达对SC - 3细胞生长发挥抑制作用的可能性。出乎意料的是，T3未能调节AIGF mRNA的表达。T3也不能显著影响雄激素刺激的SC - 3细胞中TGFβ1 mRNA的水平。更重要的是，抗TGFβ1的中和抗体不能阻断T3对雄激素诱导的SC - 3细胞生长的依赖性抑制。然而，T3的抑制能力被TGFβ1增强。此外，T3处理导致对AIGF诱导的DNA合成的显著抑制。因此，T3处理使SC - 3细胞对AIGF产生某种程度的耐受性。T3降低AIGF反应性的信号通路可能与TGFβ1共享。
