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学科主题临床医学
A human- and male-specific protocadherin that acts through the Wnt signaling pathway to induce neuroendocrine transdifferentiation of prostate cancer cells
Yang, XZ; Chen, MW; Terry, S; Vacherot, F; Chopin, DK; Bemis, DL; Kitajewski, J; Benson, NC; Guo, YL; Buttyan, R
刊名CANCER RESEARCH
2005-06-15
65期:12页:5263-5271
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]ANDROGEN DEPRIVATION THERAPY ; BETA-CATENIN MUTATIONS ; PROGNOSTIC-SIGNIFICANCE ; INDUCED APOPTOSIS ; CARCINOMA-CELLS ; UP-REGULATION ; CYCLIC-AMP ; IN-VITRO ; DIFFERENTIATION ; EXPRESSION
英文摘要

Protocadherin-PC (PCDH-PC) is a gene on the human Y chromosome that is selectively expressed in apoptosis- and hormone-resistant human prostate cancer cells. The protein encoded by PCDH-PC is cytoplasmically localized and has a small serine-rich domain in its COOH terminus that is homologous to the beta-catenin binding site of classical cadherins. Variants of prostate cancer cells that express PCDH-PC have high levels of nuclear beta-catenin protein and increased wnt-signaling. In this study, we show that transfection of human prostate cancer cells (LNCaP) with PCDH-PC or culture of these cells in androgen-free medium (a condition that up-regulates PCDH-PC expression) activates wnt signaling as assessed by nuclear accumulation of beta-catenin, increased expression of luciferase from a reporter vector promoted by Tcf binding elements and increased expression of wnt target genes. Moreover, LNCaP cells transfected with PCDH-PC or grown in androgen-free medium transdifferentiate to neuroendocrine-like cells marked by elevated expression of neuron-specific enolase and chromogranin-A. Neuroendocrine transdifferentiation was also observed when LNCaP cells were transfected by stabilized beta-catenin. Increased wnt signaling and neuroendocrine transdifferentiation of LNCaP cells induced by culture in androgen-free medium was suppressed by short interfering RNAs that target PCDH-PC as well as by dominant-negative Tcf or short interfering RNA against beta-catenin, supporting the hypothesis that increased expression of PCDH-PC is driving neuroendocrine transdifferentiation by activating wnt signaling. These findings have significant implications for the process through which prostate cancers progress to hormone resistance in humans.

语种英语
WOS记录号WOS:000229734300039
引用统计
被引频次:63[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/400002259/65628
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 100871, Peoples R China
2.Columbia Univ, Med Ctr, Dept Urol, New York, NY 10032 USA
3.Columbia Univ, Med Ctr, Dept Pathol, New York, NY 10032 USA
4.Univ Paris 12, CHU Henri Mondor, Assistance Publ Hop Paris, INSERM,Dept Urol, Creteil, France
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GB/T 7714
Yang, XZ,Chen, MW,Terry, S,et al. A human- and male-specific protocadherin that acts through the Wnt signaling pathway to induce neuroendocrine transdifferentiation of prostate cancer cells[J]. CANCER RESEARCH,2005,65(12):5263-5271.
APA Yang, XZ.,Chen, MW.,Terry, S.,Vacherot, F.,Chopin, DK.,...&Buttyan, R.(2005).A human- and male-specific protocadherin that acts through the Wnt signaling pathway to induce neuroendocrine transdifferentiation of prostate cancer cells.CANCER RESEARCH,65(12),5263-5271.
MLA Yang, XZ,et al."A human- and male-specific protocadherin that acts through the Wnt signaling pathway to induce neuroendocrine transdifferentiation of prostate cancer cells".CANCER RESEARCH 65.12(2005):5263-5271.
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