前列腺癌细胞株PC-3中PKB信号通路拮抗TGF-β信号

目的研究前列腺癌中蛋白激酶B（PKB）信号通路对转化生长因子β（TGF-β）信号通路的调节作用，探讨两信号通路在前列腺癌发生发展中的作用。方法通过生长抑制实验、细胞周期停滞实验、荧光素酶报告基因、反转录聚合酶链反应（RT-PCR）、免疫共沉淀检测PC-3细胞中PKB信号通路对TGF-β信号的调节作用。结果PKB信号通路可以抑制TGF-β反应性的CAGA报告基因活性；应用LY294002（PKB通路特异性抑制剂）可以增强TGF-β抗增殖和诱导细胞周期停滞作用；PKB信号通路的活化和抑制均不能影响TGF-β通路信号分子的表达；LY294002和TGF-β可以协同抑制cyclinD1的表达；LY294002增强TGF-β诱导的P15表达；PKB与Smad3之间存在蛋白质相互作用。结论PKB信号通路通过凋节cyclinD1和P15的表达拈抗TGF-β诱导的抗增殖和诱导细胞周期停滞作用，Smad3与PKB的相互作用可能介导了该作用。PKB信号通路通过上述拈抗性作用促进了前列腺癌的发生发展。

Role of PKB pathway in regulating antiproliferative effect induced by TGF-β

Objective To investigate the role of PKB pathway in regulating antiproliferative effect induced by TGF-β. Methods Growth arrest, cell cycle arrest, luciferase reporter assay, RT-PCR, ilnmunoprieipitation were done to explore the regulation of TGF-β signaling by PKB signaling pathway. Results PKB pathway inhibited TGF-β signaling using TGF-β responsive CAGA luciferase reporter. Inhibition of PKB pathway promoted antiproliferative effect and cell cycle arrest induced by TGF-β. Inhibition of PKB pathway enhanced the ability of TGF-β to downregulate the promoter activity of cyclinDl and upregulate P15 expression. PKB pathway inhibited TGF-β signaling. PKB pathway did not regulate the expression of TGF-β signaling molecules. PKB is interrelated to Smad3. Conclusions PKB pathway inhibits TGF-β signaling especially the antiproliferative effect induced by TGF-β. This effect may partly through PKB and Smad3 interaction. Through this antiproliferative effect, PKB pathway may take part in the development and progress of prostate carcinoma.