Mukai M, Endo H, Iwasaki T, Tatsuta M, Togawa A, Nakamura H, Inoue M
Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
Biochem Biophys Res Commun. 2006 Jul 21;346(1):74-82. doi: 10.1016/j.bbrc.2006.05.068. Epub 2006 May 19.
Transforming growth factor-beta1 (TGF-beta1) is a multifunctional growth factor that plays a role in cell proliferation, differentiation, extracellular matrix production, apoptosis, and cell motility. We show here that TGF-beta1 increased the invasiveness of MM1 cells, which are a highly invasive clone of rat ascites hepatoma cells. Both mRNA and protein levels of RhoC but not RhoA in TGF-beta1-treated MM1 cells increased. In parallel with this increase in expression, RhoC activity was induced by TGF-beta1 treatment. When RhoC was overexpressed in MM1 cells, the invasive capacity increased. The RhoC-overexpressing cells formed more nodules than did mock cells when injected into rat peritoneum. Furthermore, when RhoC expression was reduced by transfection with shRNA/RhoC, the invasiveness of MM1 cells decreased with concomitant suppression of RhoC expression. Thus, the induced expression of RhoC by TGF-beta1 in MM1 cells plays a critical role in TGF-beta1-induced cell migration.
转化生长因子-β1（TGF-β1）是一种多功能生长因子，在细胞增殖、分化、细胞外基质产生、细胞凋亡和细胞运动中发挥作用。我们在此表明，TGF-β1增加了MM1细胞的侵袭性，MM1细胞是大鼠腹水肝癌细胞的一个高侵袭性克隆。在TGF-β1处理的MM1细胞中，RhoC的mRNA和蛋白水平增加，而RhoA则没有。与这种表达增加同时，TGF-β1处理诱导了RhoC活性。当RhoC在MM1细胞中过表达时，侵袭能力增加。将过表达RhoC的细胞注射到大鼠腹膜中时，形成的结节比对照细胞更多。此外，当用shRNA/RhoC转染降低RhoC表达时，MM1细胞的侵袭性降低，同时RhoC表达受到抑制。因此，TGF-β1在MM1细胞中诱导的RhoC表达在TGF-β1诱导的细胞迁移中起关键作用。
