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Analysis and detection of the molecules involving hormone refractory prostate cancer by applying Proteomics methodology

应用蛋白质组学方法分析检测激素难治性前列腺癌相关分子

基本信息

批准号：
14370517
负责人：
KUBOTA Yoshinobu
金额：
$ 9.15万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

To analyze the key molecules involving progression of prostate cancer to hormone refractory cancer, we have applied proteomics and other molecular biological methodologies in this research project.We have identified several molecules which expressed diffentially between androgen dependent prostate cancer cells and androgen independent ones in 2D gel analysis by applying anti-body to tyrosin-kinase. We, then, have focused on the Angiotensin II receptor (AT1) molecules among them.We demonstrated that AT1 receptar is expressed in human prostate cells. Especially, high expression level of AT1 receptor is seen in androgen independent prostate cancer cells. And stimulation by AII induces activation of intracellular signal transduction pathways that lead to the growth of prostate cancer cells. And we showed that candesartan, an angiatensin II receptor (AT1) blocker, inhibits both the growth of prostate cancer calls in vitro and that of tumors produced by prostate cancer cells in nude mice in vivo (Mol cancer Therap. 2003). We also suggested the potential of AT1 receptor blocker as a novel therapy for prostate cancer (J. Urol. 2005).We think that these study results have made a remarkable contribution to elucidate the mechanisms of hormone refractory prostate cancer as well as to develop a new novel therapy for this disease.

本研究采用蛋白质组学等分子生物学方法，通过应用酪氨酸激酶抗体进行二维凝胶电泳，筛选出雄激素依赖性前列腺癌细胞和雄激素非依赖性前列腺癌细胞之间差异表达的分子，以分析前列腺癌向激素难治性前列腺癌发展的关键分子。我们对其中的血管紧张素Ⅱ受体（AngiotensinII receptor，AT 1）分子进行了研究，证实AT 1受体在人前列腺细胞中有表达。特别是在雄激素非依赖性前列腺癌细胞中，AT1受体的高表达水平。AII的刺激诱导细胞内信号转导途径的激活，导致前列腺癌细胞的生长。我们发现坎地沙坦，一种血管紧张素II受体（AT 1）阻断剂，在体外抑制前列腺癌细胞的生长，在体内抑制前列腺癌细胞在裸鼠中产生的肿瘤的生长（Mol cancer Therap. 2003年）。我们还提出了AT1受体阻滞剂作为前列腺癌新疗法的潜力（J. Urol.我们认为这些研究结果对于阐明激素难治性前列腺癌的发病机制以及开发治疗该疾病的新方法做出了显著贡献。