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

为了分析前列腺癌向激素难治性癌发展的关键分子，我们在本项目中应用了蛋白质组学等分子生物学方法。我们利用酪氨酸激酶抗体在二维凝胶分析中发现了雄激素依赖性和雄激素非依赖性前列腺癌细胞之间表达差异的几个分子。因此，我们将重点放在其中的血管紧张素II受体（AT1）分子上。我们证实AT1受体在人前列腺细胞中表达。特别是在雄激素不依赖型前列腺癌细胞中，AT1受体的表达水平较高。AII的刺激会激活细胞内信号转导通路，从而导致前列腺癌细胞的生长。我们发现坎地沙坦，一种血管生成素II受体（AT1）阻滞剂，在体外抑制前列腺癌细胞的生长和体内裸鼠前列腺癌细胞产生的肿瘤的生长（Mol cancer therapy . 2003）。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. 2005）。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新的治疗方法具有重要的意义。

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.