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学科主题临床医学
Complex regulation of human androgen receptor expression by Wnt signaling in prostate cancer cells
Yang, X; Chen, MW; Terry, S; Vacherot, F; Bemis, DL; Capodice, J; Kitajewski, J; de la Taille, A; Benson, MC; Guo, Y; Buttyan, R
关键词androgen receptor Wnt signaling beta-catenin PCDH-PC Akt MDM2
刊名ONCOGENE
2006-06-08
DOI10.1038/sj.onc.1209366
25期:24页:3436-3444
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
研究领域[WOS]Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
关键词[WOS]BETA-CATENIN MUTATIONS ; MEDIATED TRANSCRIPTION ; PATHWAY ; GENE ; AKT ; INDEPENDENCE ; PROGRESSION ; ACTIVATION ; PHOSPHORYLATION ; GROWTH
英文摘要

beta-Catenin, a component of the Wnt signaling pathway, is a coactivator of human androgen receptor (hAR) transcriptional activity. Here, we show that Wnt signaling also influences androgen-mediated signaling through its ability to regulate hAR mRNA and protein in prostate cancer (PCa) cells. Three functional LEF-1/TCF binding sites lie within the promoter of the hAR gene as shown by CHIP assays that captured beta-catenin-bound chromatin from Wnt-activated LNCaP cells. Chimeric reporter vectors that use the hAR gene promoter to drive luciferase expression confirmed that these LEF-1/TCF binding elements are able to confer robust upregulation of luciferase expression when stimulated by Wnt-1 or by transfection with beta-catenin and that dominant-negative TCF or mutations within the dominant TCF-binding element abrogated the response. Semi-quantitative and real time RT-PCR assays confirmed that Wnt activation upregulates hAR mRNA in PCa cells. In contrast, hAR protein expression was strongly suppressed by Wnt activation. The reduction of hAR protein is consistent with evidence that Wnt signaling increased phosphorylation of Akt and its downstream target, MDM2 that promotes degradation of hAR protein through a proteasomal pathway. These data indicate that the hAR gene is a direct target of LEF-1/TCF transcriptional regulation in PCa cells but also show that the expression of the hAR protein is suppressed by a degradation pathway regulated by cross-talk of Wnt to Akt that is likely mediated by Wnt-directed degradation of the B regulatory subunit of protein phosphatase, PP2A.

语种英语
WOS记录号WOS:000238448100008
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被引频次:68[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60323
专题北京大学第一临床医学院_泌尿外科
作者单位1.Columbia Univ, Dept Urol, Med Ctr, New York, NY 10032 USA
2.Columbia Univ, Med Ctr, Dept Pathol, New York, NY USA
3.Peking Univ, Hosp 1, Dept Urol, Beijing, Peoples R China
4.Univ Paris 12, AP HP, CHU Henri Mondor, INSERM,E03 37, Creteil, France
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GB/T 7714
Yang, X,Chen, MW,Terry, S,et al. Complex regulation of human androgen receptor expression by Wnt signaling in prostate cancer cells[J]. ONCOGENE,2006,25(24):3436-3444.
APA Yang, X.,Chen, MW.,Terry, S.,Vacherot, F.,Bemis, DL.,...&Buttyan, R.(2006).Complex regulation of human androgen receptor expression by Wnt signaling in prostate cancer cells.ONCOGENE,25(24),3436-3444.
MLA Yang, X,et al."Complex regulation of human androgen receptor expression by Wnt signaling in prostate cancer cells".ONCOGENE 25.24(2006):3436-3444.
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