Yoo Y D, Choi J Y, Lee S J, Kim J S, Min B R, Lee Y I, Kang Y K
Laboratory of Experimental Therapeutics and Korea Cancer Center Hospital, Seoul, Republic of Korea.
Int J Cancer. 1999 Nov 12;83(4):512-7. doi: 10.1002/(sici)1097-0215(19991112)83:4<512::aid-ijc13>3.0.co;2-z.
Transforming growth factor-beta1 (TGF-beta) inhibits cell-cycle progression of many types of cells by arresting them in G(1)/S phase through inhibition of the active cyclin-Cdk complexes that lead to inhibition of Rb phosphorylation. In gastric-cancer cells, SNU16, TGF-beta treatment induced enhanced expression of p21(WAF1/CIP1) (p21), which inhibited the kinase activity of cyclin-D- and cyclin-E-associated Cdks and blocked p130 phosphorylation. TGF-beta also enhanced the stability of p130, suggesting that hypophosphorylation of p130 and increased stability of p130 contribute to p130-mediated G(1) arrest in gastric-cancer cells. Our results demonstrate that p21 and p130 are major downstream targets of TGF-beta in gastric-cancer cells and that a p21-G(1) cyclin/Cdks-p130/E2F pathway mediates growth inhibition by TGF-beta in these cells.
转化生长因子-β1（TGF-β）通过抑制活性细胞周期蛋白-Cdk复合物，使细胞停滞在G(1)/S期，从而抑制多种类型细胞的细胞周期进程，这种抑制会导致Rb磷酸化受到抑制。在胃癌细胞SNU16中，TGF-β处理可诱导p21(WAF1/CIP1)（p21）表达增强，p21抑制了细胞周期蛋白D和细胞周期蛋白E相关Cdk的激酶活性，并阻断了p130磷酸化。TGF-β还增强了p130的稳定性，这表明p130的低磷酸化和p130稳定性的增加有助于p130介导的胃癌细胞G(1)期停滞。我们的结果表明，p21和p130是胃癌细胞中TGF-β的主要下游靶点，并且p21-G(1)细胞周期蛋白/Cdks-p130/E2F途径介导了TGF-β对这些细胞的生长抑制作用。
