Androgen suppresses proliferation of castration-resistant LNCaP 104-R2 prostate cancer cells through androgen receptor, Skp2, and c-Myc

NCU Institutional Repository > 生醫理工學院 > 生命科學系 > 期刊論文 > Item 987654321/50794

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://ir.lib.ncu.edu.tw/handle/987654321/50794

题名:	Androgen suppresses proliferation of castration-resistant LNCaP 104-R2 prostate cancer cells through androgen receptor, Skp2, and c-Myc
作者:	Chuu,CP;Kokontis,JM;Hiipakka,RA;Fukuchi,J;Lin,HP;Lin,CY;Huo,C;Su,LC;Liao,SS
贡献者:	生命科學系
关键词:	ANTIGEN MESSENGER-RNA;DEPRIVATION THERAPY;ATHYMIC MICE;TUMOR-GROWTH;TESTOSTERONE REPLACEMENT;CARDIOVASCULAR-DISEASE;GENE AMPLIFICATION;CYCLE ARREST;PROGRESSION;EXPRESSION
日期:	2011
上传时间:	2012-03-27 18:10:17 (UTC+8)
出版者:	國立中央大學
摘要:	Androgen ablation therapy is the primary treatment for metastatic prostate cancer. However, this therapy is associated with several undesired side-effects, including increased risk of cardiovascular diseases. To study if termination of long-term androgen ablation and restoration of testosterone levels could suppress the growth of relapsed hormone-refractory prostate tumors, we implanted testosterone pellets in castrated nude mice carrying androgen receptor (AR)-positive LNCaP 104-R2 cells, which relapsed from androgen-dependent LNCaP 104-S cells after long-term androgen deprivation. 104-R2 tumor xenografts regressed after testosterone pellets were implanted. Of 33 tumors, 24 adapted to elevation of testosterone level and relapsed as androgen-insensitive tumors. Relapsed tumors (R2Ad) expressed less AR and prostate-specific antigen. We then studied the molecular mechanism underlying the androgenic regulation of prostate cancer cell proliferation. Androgen suppresses proliferation of 104-R2 by inducing G(1) cell cycle arrest through reduction of S-phase kinase-associated protein 2 (Skp2) and c-Myc, and induction of p27(Kip1). 104-R2 cells adapted to androgen treatment and the adapted cells, R2Ad, were androgen-insensitive cells with a slower growth rate and low protein level of AR, high levels of c-Myc and Skp2, and low levels of p27(Kip1). Nuclear AR and prostate-specific antigen expression is present in 104-R2 cells but not R2Ad cells when androgen is absent. Overexpression of AR in R2Ad cells regenerated an androgen-repressed phenotype; knockdown of AR in 104-R2 cells generated an androgen-insensitive phenotype. Overexpression of Skp2 and c-Myc in 104-R2 cells blocked the growth inhibition caused by androgens. We concluded that androgens cause growth inhibition in LNCaP 104-R2 prostate cancer cells through AR, Skp2, and c-Myc. (Cancer Sci 2011; 102: 2022-2028)
關聯:	CANCER SCIENCE
显示于类别:	[生命科學系] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
index.html		0Kb	HTML	650	检视/开启

在NCUIR中所有的数据项都受到原著作权保护.

社群 sharing

数据加载中.....