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Mechanism of loss of androgen dependency in prostate cancer, related to its proliferation and expansion

前列腺癌雄激素依赖性丧失的机制与其增殖和扩张有关

基本信息

批准号：
10470335
负责人：
KAWAMURA Juichi
金额：
$ 8.32万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470335/
关键词：
prostate cancer hormone-refractory cancer genetic polymorphism immunostain of Ki-67 chromosome 8p α6 integrin Sp1 MAP kinase アンドロゲン依存性アンドロゲン非依存性インテグリン MAPキナーゼマップカイネース代謝酵素 comperative glnomic hybridization

项目摘要

The results of the research project are as follows :1. Anaysis of genetic polymorphisms which may play an important role in individual susceptability with regard to prostate cancer development. 1) CYP 1A1 among catalyzing enzymes in the phase 1 and NAT1 among conjugating enzymes in the phase 2 had a significantly higher risk of prostate cancer. Moreover, combination of CYP 1 and GSTM1, one of conjugating enzyme groups, increased the risk of prostate cancer development. 2) A higher frequency of CYP 17, an enzyme gene involved in steroid metabolism, was associated with the higher risk of prostate cancer.2. Immunohistochemical analysis using expressions of Ki-67 antigen, bc1-2 and p53 oncoproteins to predict disease progression in prostate cancer. Ki-67 labeling index was the most useful parameter to predict PSA failure or the advanced prostate cancer after the initial endocrine therapy.3. Molecular genetic analysis of chromosome 8p in prostate cancer patients. Frequent loss of heterozygosity was observed for D8S201 (48%), LPL (48%) and DCC(26%). Microsatellite instability was observed in 28% in stages B, C and D.Unidentified genes on chromosome 8p may be involved in carcinogenesis of the prostate.4. Investigation of mitogen-activated protein kinases (MAP kinase) pathway involving in the α6 integrin gene expression in androgen-independent prostate cancer cell lines. Sp1 consensus sequence at -48 to 43 bp from the transcription start site was necessary for basal promoter activity of the α6 integrin, suggesting that signal transduction from MAP kinases to activation of Sp1 might involved in α6 integrin expression in androgen-independent prostate cancer cell lines.

本课题的主要研究成果如下：1.分析遗传多态性可能在前列腺癌发展的个体易感性中起重要作用。1)在第一阶段的催化酶中，NAT 1A 1和在第二阶段的结合酶中，NAT 1具有显著更高的前列腺癌风险。此外，结合酶组之一的GSTM 1和GSTM 1的组合增加了前列腺癌发展的风险。2)参与类固醇代谢的一种酶基因-β 17的高频率与前列腺癌的高风险相关。利用Ki-67抗原、bc 1 -2和p53癌蛋白表达的免疫组织化学分析预测前列腺癌的疾病进展Ki-67标记指数是预测初次内分泌治疗后PSA失败或晚期前列腺癌最有用的参数.前列腺癌患者染色体8 p的分子遗传学分析。D8 S201、LPL和DCC的杂合性丢失率分别为48%、48%和26%。B、C、D期患者中28%存在微卫星不稳定性，染色体8 p上的未知基因可能参与前列腺癌的发生.雄激素非依赖性前列腺癌细胞系α6整合素基因表达中丝裂原活化蛋白激酶（MAP激酶）通路的研究α6整合素的基础启动子活性需要转录起始位点-48 ~43 bp的Sp1共有序列，提示在雄激素非依赖性前列腺癌细胞系中，α 6整合素的表达可能与MAP激酶的信号转导和Sp1的激活有关。