Identification of metastasis suppressor genes for prostate cancer and analysis of genetic changes during progression of prostate cancer.

鉴定前列腺癌转移能力的分子和细胞标记物将有助于开发组织学上局限性前列腺癌的亚分期诊断方法。为了分离转移抑制基因，我们建立了一个大鼠前列腺癌系统。在这个系统中，我们使用微细胞介导的染色体转移技术将正常染色体的单拷贝导入高转移的大鼠前列腺癌。在以前的研究中，我们从11p11.2中分离了前列腺癌转移抑制基因KAI1/CD82。我们还证明了KAI1/CD82在人类前列腺癌的发展过程中表达下调。在本研究中，我们证明了这种下调不需要KAI1/CD82的缺失或点突变。用同样的方法，我们报道了另一个转移抑制基因位于人类染色体8p21-p12区域。在目前的研究中，这个区域已经缩小到大约1 cM，这与在人类前列腺癌中经常观察到杂合性缺失(LOH)的区域重叠。我们目前正在构建覆盖这个1 cM区域的BAC重叠群图。我们还发表了人类7号和12号染色体包含前列腺癌转移抑制基因。我们还发表了人类19号染色体包含前列腺癌的肿瘤抑制基因。人类13号染色体在不抑制大鼠前列腺癌致瘤性的情况下降低了转移能力。我们已经在人类前列腺癌中进行了LOU分析，并表明13q14与转移有关，这一研究已经发表。

Identification of molecular and cellular markers for the metastatic ability of prostate cancer would be useful in developing diagnostic methods for substaging histologically localized prostate cancers. To isolate metastasis suppressor genes, we have established a rat prostate cancer system. In this system, we used a microcell mediated chromosome transfer technique to introduce a single copy of normal human chromosomes into highly metastatic rat prostate cancer.In the previous studies, we isolated KAI1/CD82, a metastasis suppressor gene for prostate cancer, from 11p11.2. We also demonstrated that KAI1/CD82 was down- regulated during the progression of human prostate cancer. In the present study, we demonstrate that this down regulation does not require either deletion or point mutation of KAI1/CD 82.By using the same method, we reported that another metastasis suppressor gene was located on the human chromosome region 8p21-p12. In the present study, this region has been narrowed down to about 1 cM.This is overlapped to the regon where loss of heterozygosity (LOH) has been observed frequently in human prostate cancer We are currently constructing a BAC contig map that covers this 1 cM region.We have also published that human chromosomes 7 and 12 contain metastasis suppressor genes for prostate cancer. We have also published that human chromosome 19 contains a tumor suppressor gene for prostate cancer.Human chromosome 13 reduces metastatic ability without suppression of tumorigenicity of rat prostate cancer. We have performed LOU analysis in the human prostate cancer and have shown that the 13q14 is associated with metastasis, which has been published.