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ROLE OF INTEGRIN AND EXTRACELLULAR MATRIX IN PROLIFERATION AND METASTASIS OF PROSTATE CANCER AND INVESTIGATION OF MODULATION FACTORS

整合素和细胞外基质在前列腺癌增殖和转移中的作用及调节因子的研究

基本信息

批准号：
07457369
负责人：
KAWAMURA Juichi
金额：
$ 4.48万
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：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

This is a final stage of our research project during three years. We have almost finished our experiments of isolation of mRNA of alpha6 integrin and its expression in androgen-sensitive or androgen-insensitive LNCaP prostate cell lines. As one of our experimental results, it was found that Dihydrotestosterone (DHT) combines with the androgen receptor in LNCaP cells, followed by combining with the androgen response element, and DHT down-regulates alpha6 integrin gene expression. On the contrary, DHT-androgen receptor complex up-regulates alpha6 integrin gene expression via induction of protein synthesis.In the next step, we would like to investigate an effect of DHT on alpha6 integrin gene expression on the level of protein syntheis using immunoprecipitation method, and to investigate a higher migration ability of LNCaP cells which expresses the large amount of alpha6 integrin genes using matrigel invasion chamber.An acquisition of androgen-insensitivity by prostate cancer cells is a result of induction of protein synthesis via DHT-androgen receptor complex. This study shows that the mechanism driven by androgen in androgen-sensitive cells might be conserved in androgen-insensitive cells. This indicates that the expression of alpha6 integrin mRNA inhibited by androgen remained unchanged in androgen-sensitive and -insensitive cells.

这是我们三年研究项目的最后阶段。我们已经基本完成了α 6整合素mRNA的分离及其在雄激素敏感或雄激素不敏感的LNCaP前列腺细胞株中的表达实验。我们的实验结果发现，在LNCaP细胞中，双氢睾酮（DHT）与雄激素受体结合，随后与雄激素应答元件结合，DHT下调alpha6整合素基因表达。相反，dht雄激素受体复合体通过诱导蛋白合成上调α 6整合素基因表达。下一步，我们将利用免疫沉淀法在蛋白合成水平上研究DHT对alpha6整合素基因表达的影响，并利用matrigel侵袭室研究大量表达alpha6整合素基因的LNCaP细胞具有更高的迁移能力。前列腺癌细胞获得雄激素不敏感是通过dht -雄激素受体复合物诱导蛋白质合成的结果。本研究表明雄激素敏感细胞中雄激素驱动的机制可能在雄激素不敏感细胞中保守。这表明受雄激素抑制的α 6整合素mRNA的表达在雄激素敏感细胞和雄激素不敏感细胞中保持不变。