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前列腺癌对TGF-β诱导的生长抑制不敏感,而PI3K-PKB信号通路在大多数前列腺癌中高度活化．通过生长抑制实验和荧光素酶报告基因系统发现,PI3K-PKB信号通路抑制前列腺癌细胞PC-3对TCF-β诱导的生长抑制和细胞周期停滞的反应;PI3K—PKB信号通路抑制TGF-β诱导的基因转录．免疫共沉淀结果显示,PKB与Smad3之间存在蛋白质相互作用,两者之间的相互作用是通过Smad3的MH2和Linker结构域介导的;TGF-β减弱PKB与Smad3的结合,胰岛素(模拟PKB活化)增强两者的结合;PKB与Smad3的结合是PKB激酶活性依赖的,丧失激酶活性的PKB不能与Smad3相互作用．结果表明,前列腺肿瘤丧失对TGF-β的敏感性与PI3K-PKB信号通路的过度活化明显相关．PI3K—PKB信号通路通过PKB与Smad3的结合抑制TGF-β诱导的生长抑制和基因转录．
Prostate cancer is not sensitive to TGF-β-induced growth inhibition, whereas the PI3K-PKB signaling pathway is highly activated in most prostate cancers. The PI3K-PKB signaling pathway inhibited the growth inhibition and cell cycle arrest induced by TCF-β in prostate cancer cell line PC-3 through inhibition of growth and luciferase reporter system. PI3K-PKB signaling pathway inhibited the induction of TGF-β Gene transcription. Co-immunoprecipitation showed that there was protein interaction between PKB and Smad3, and the interaction between them was mediated through the MH2 and Linker domains of Smad3; TGF-β attenuated the binding of PKB to Smad3, insulin (mimicking PKB Activation) enhance the combination of the two; PKB binding to Smad3 PKB kinase activity-dependent, loss of kinase activity of PKB and Smad3 can not interact. The results show that the loss of prostate cancer sensitivity to TGF-β and PI3K-PKB signaling pathway over-activation was significantly correlated. The PI3K-PKB signaling pathway inhibits TGF-β-induced growth inhibition and gene transcription through binding of PKB to Smad3.