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学科主题: 临床医学
题名:
PKB negatively modulates TGF-beta responsiveness in prostate carcinoma PC-3 cells through its interaction with Smad3
作者: 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
发表日期: 2006-07-01
DOI: 10.1007/s11434-006-2016-1
卷: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59736
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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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

Recommended Citation:
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.
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