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PKB negatively modulates TGF-β responsiveness in prostate carcinoma PC-3 cells through its interaction with Smad3

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Chinese Science Bulletin

Abstract

Most prostate cancers are insensitive to growth-inhibitory effect of TGF-β, while PI3K-PKB signaling is highly activated in prostate cancers. We investigated whether the PI3K-PKB signaling contributes to TGF-β insensitivity in PTEN-null prostate cancer PC-3 cells. Cell growth analysis showed that inhibition of PI3K-PKB pathway by LY294002 enhanced growth inhibition and cell cycle arrest induced by TGF-β. Furthermore, activation of PI3K-PKB pathway by insulin or overexpression of PKB decreased the transcriptional activity of TGF-β, as measured by the TGF-β/Smad3-responsive CAGA-luciferase reporter, while inhibition of PI3K-PKB pathway by introducing PTEN, inactive PKB mutant or using LY294002 promoted TGF-β-induced expression of CAGA-luciferase. Co-immunoprecipitation studies further demonstrated that Smad3 interacted with PKB through its linker region and MH2 domain. This interaction was facilitated by insulin and disrupted by TGF-β signaling activation. Our results suggest that the PI3K-PKB pathway may play an important role in rendering cell resistance to the antiproliferative effect of TGF-β and regulating cell response to TGF-β.

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Authors and Affiliations

  1. Department of Urology, the First Hospital of Peking University, Beijing, 100034, China

    Li Wei, Xin Dianqi & Guo Yinlu

  2. the Urological Research Institute, Peking University, Beijing, 100034, China

    Li Wei, Xin Dianqi & Guo Yinlu

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  1. Li Wei
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  2. Xin Dianqi
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  3. Guo Yinlu
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Correspondence to Guo Yinlu.

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Li, W., Xin, D. & Guo, Y. PKB negatively modulates TGF-β responsiveness in prostate carcinoma PC-3 cells through its interaction with Smad3. CHINESE SCI BULL 51, 1563–1570 (2006). https://doi.org/10.1007/s11434-006-2016-1

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  • DOI: https://doi.org/10.1007/s11434-006-2016-1

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