Study of the Identification of new genes associated with development and recurrence of prostate cancer

前列腺癌是西方国家最常见的肿瘤之一。这种疾病的分子背景仍不清楚。因此，我们对端粒酶基因在前列腺癌中的表达进行了研究，并应用差异显示聚合酶链式反应(Differential Display PCR，DD-PCR)分析了前列腺癌组织和活检组织中的端粒酶活性。结果表明，端粒酶基因在前列腺癌中的表达是一致的。检测活检组织中端粒酶活性可作为前列腺癌的诊断指标。2)对双氢睾酮(DHT)处理的LNCaP细胞、癌组织和正常前列腺组织的RNA进行差异表达基因分析。利用DD-PCR技术，我们鉴定了DHT在LNCaP细胞中下调和上调的c DNA片段。此外，还鉴定了癌组织中特异表达的c-DNA。序列分析表明，该片段与蛋白质酪氨酸磷酸酶相关基因Liprin-α2完全相同。双氢睾酮对Liprin-α2的下调作用具有时间和雄激素浓度依赖性。该基因在雄激素非依赖性前列腺癌PC-3和DU-145细胞中不表达。本研究还鉴定了NKX3.1样基因、OSM-β等基因为前列腺癌相关基因，提示Liprin-α2受雄激素直接调控，该基因表达缺失可能与前列腺癌向雄激素非依赖性发展有关。进一步的分析正在进行中，以澄清前列腺癌中发现的其他基因的功能。

Prostate cancer is one of the most common neoplasms in the Western country. Molecular background of this disease is still unclear. Thus, We studied the expression of telomerase gene in prostate cancer as one of new genes and also, We applied differential display PCR (DD-PCR) to identify androgen-regulated and prostate cancer specific genes in prostate cancer.1) Telomerase activity was analyzed in prostate cancer tissyues and biopsy samples using PCR based TRAP assay. As a results, expression of telomerase gene was consistent among the cancer of prostate. And detecting telomerase activity in biopsy sample could be useful as a diagnostic marker for prostate ccncer.2) The RNA of LNCaP cells treated with dihydrotestosterone (DHT), and RNA from cancer tissues and normal prostate tissues from same patients were analyzed for differentially expressed genes. Using DD-PCR, we identified down regulated and up-regulated cDNA fragment by DHT in LNCaP cells. And also c-DNA specifically expressed in cancer tissues were identified. These fragments were then sequenced.Sequence analysis revealed that a cDNA fragment as one of interesting genes is identical to protein tyrosine phosphatase LAR related gene, liprin -α2. Liprin -α2 was downregulated by dihydrotestosterone (DHT) in LNCaP cells in a time- and androgen concentration-dependent manner. This gene was not expressed in androgen independent prostate cell lines PC-3 and DU-145 at the mRNA level. We have also identified NKX 3.1 like gene, OSM-beta and other genes as prostate cancer asoociated genes in this research.These data suggest that liprin-α2 is directly regulated by androgens and the loss of this gene expression might be associated with progression of prostate cancer to androgen independence. Further analysis are on going for clarify the function of other genes identified in prostate cancer.