权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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

与前列腺癌发生和复发相关的新基因的鉴定研究

基本信息

批准号：
08457428
负责人：
KUBOTA Yoshinobu
金额：
$ 4.22万
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：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

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.

前列腺癌是西方国家最常见的肿瘤之一。该病的分子背景尚不清楚。因此，本研究将端粒酶基因作为一个新的基因，在前列腺癌中进行研究，并应用差异显示PCR（DD-PCR）技术，对前列腺癌中雄激素调节基因和前列腺癌特异性基因进行鉴定。1）采用PCR-TRAP法检测前列腺癌组织和前列腺癌活检标本中端粒酶活性。结果表明，端粒酶基因在前列腺癌中的表达具有一致性。检测前列腺活检组织中端粒酶活性可作为前列腺癌的诊断标志物。2）对经双氢睾酮（DHT）处理的LNCaP细胞的RNA以及来自同一患者的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，我们在LNCaP细胞中鉴定了DHT下调和上调的cDNA片段。并鉴定了癌组织中特异性表达的c-DNA。序列分析表明，其中一个cDNA片段与蛋白酪氨酸磷酸酶LAR相关基因liprin -α2完全相同。二氢睾酮（DHT）以时间和雄激素浓度依赖性方式下调LNCaP细胞Liprin -α2的表达。该基因在雄激素非依赖性前列腺细胞系PC-3和DU-145中不表达。本研究还发现NKX3.1like基因、OSM-beta等前列腺癌相关基因，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，以澄清在前列腺癌中鉴定的其他基因的功能。