Targeting tyrosine phosphorylation of PCNA inhibits prostate cancer growth

ASIA unversity > 醫學暨健康學院 > 生物科技學系 > 期刊論文 > Item 310904400/16211

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://asiair.asia.edu.tw/ir/handle/310904400/16211

题名:	Targeting tyrosine phosphorylation of PCNA inhibits prostate cancer growth
作者:	洪明奇;Hung, Mien-Chie
贡献者:	生物科技學系
日期:	2011
上传时间:	2012-11-23 09:09:59 (UTC+0)
摘要:	The proliferation cell nuclear antigen (PCNA) is a critical protein required for DNA replication in proliferating cells including cancer cells. However, direct inhibition of PCNA in cancer cells has been difficult due to the lack of targetable sites. We previously reported that phosphorylation of tyrosine 211 (Y211) on PCNA is important for the proliferative function of PCNA when this protein is associated with the chromatin in cancer cells. Here, we show that the Y211 phosphorylation of PCNA is a frequent event in advanced prostate cancer. To explore the potential of this signaling event in inhibition of cancer cell growth, we used a synthetic peptide, the Y211F peptide, which when present inhibits phosphorylation of Y211 on endogenous PCNA. Treatment with this peptide, but not a scrambled control peptide, resulted in S-phase arrest, inhibition of DNA synthesis, and enhanced cell death in a panel of human prostate cancer cell lines. In addition, treatment with the Y211F peptide led to decreased tumor growth in PC3-derived xenograft tumors in vivo in nude mice. Our study shows for the first time that PCNA phosphorylation at Y211 is a frequent and biologically important signaling event in prostate cancer. This study also shows a proof of concept that Y211 phosphorylation of PCNA may be used as a therapeutic target in prostate cancer cells, including cells of advanced cancers that are refractory to standard hormonal therapies.
關聯:	MOLECULAR CANCER THERAPEUTICS
显示于类别:	[生物科技學系] 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	395	检视/开启
index.html		0Kb	HTML	297	检视/开启

在ASIAIR中所有的数据项都受到原著作权保护.

数据加载中.....