IR@PKUHSC  > 北京大学第一临床医学院  > 泌尿外科
学科主题临床医学
PKB negatively modulates TGF-beta responsiveness in prostate carcinoma PC-3 cells through its interaction with Smad3
Li, Wei; Xin, Dianqi; Guo, Yinlu
关键词prostate carcinoma protein kinase B transforming growth factor beta Smad3 protein interaction
刊名CHINESE SCIENCE BULLETIN
2006-07-01
DOI10.1007/s11434-006-2016-1
51期:13页:1563-1570
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]GROWTH-FACTOR-BETA ; CANCER CELLS ; ACTIVATION ; AKT ; RAPAMYCIN ; LINES
英文摘要

Most prostate cancers are insensitive to growth-inhibitory effect of TGF-beta, while PI3K-PKB signaling is highly activated in prostate cancers. We investigated whether the PI3K-PKB signaling contributes to TGF-beta 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-beta. Furthermore, activation of PI3K-PKB pathway by insulin or overexpression of PKB decreased the transcriptional activity of TGF-beta, as measured by the TGF-beta/Smad3-responsive CAGA-luciferase reporter, while inhibition of PI3K-PKB pathway by introducing PTEN, inactive PKB mutant or using LY294002 promoted TGF-beta-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-beta 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-beta and regulating cell response to TGF-beta.

语种英语
WOS记录号WOS:000240487600006
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59736
专题北京大学第一临床医学院_泌尿外科
作者单位1.Peking Univ, Hosp 1, Dept Urol, Beijing 100034, Peoples R China
2.Peking Univ, Urol Res Inst, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Li, Wei,Xin, Dianqi,Guo, Yinlu. PKB negatively modulates TGF-beta responsiveness in prostate carcinoma PC-3 cells through its interaction with Smad3[J]. CHINESE SCIENCE BULLETIN,2006,51(13):1563-1570.
APA Li, Wei,Xin, Dianqi,&Guo, Yinlu.(2006).PKB negatively modulates TGF-beta responsiveness in prostate carcinoma PC-3 cells through its interaction with Smad3.CHINESE SCIENCE BULLETIN,51(13),1563-1570.
MLA Li, Wei,et al."PKB negatively modulates TGF-beta responsiveness in prostate carcinoma PC-3 cells through its interaction with Smad3".CHINESE SCIENCE BULLETIN 51.13(2006):1563-1570.
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