Kawana Y, Komiya A, Ueda T, Nihei N, Kuramochi H, Suzuki H, Yatani R, Imai T, Dong J T, Imai T, Yoshie O, Barrett J C, Isaacs J T, Shimazaki J, Ito H, Ichikawa T
Department of Urology, Chiba University School of Medicine, Japan.
Prostate. 1997 Aug 1;32(3):205-13. doi: 10.1002/(sici)1097-0045(19970801)32:3<205::aid-pros7>3.0.co;2-j.
We recently isolated the KAI1 gene, a metastasis suppressor gene for prostate cancer, from human chromosome region 11p13-cen-containing rat prostate cancer cells. The present study was performed to further locate the region of the KAI1 gene on the short arm of chromosome 11, and to examine whether loss of this region is significant during progression of human prostate cancer.
The small portion of human chromosome 11 (i.e., 11p13-cen) was reintroduced into highly metastatic rat prostate cancer cells by using microcell-mediated chromosome transfer. Loss of heterozygosity (LOH) at polymorphic microsatellite loci on the human chromosome 11 was examined in human prostate cancer tissues.
The minimum region of human chromosome 11 that contained the KAI1 gene was located on the proximal region of 11p11.2 divided by the D11S554 locus. The percentage of LOH or allelic imbalance at the D11S1344 locus, which is located on the same region as the KAI1 locus, in metastasis tissues from autopsy cases who died from metastatic prostate cancer was 70% (7 of 10 informative cases), whereas the percentages in primary tumors from the same cases and from cases with clinically localized prostate cancer were 33% (3 of 9 informative cases) and 8% (1 of 12 informative cases), respectively.
These findings demonstrate a high frequency of LOH or allelic imbalance at the centromeric region of 11p, which contains the KAI1 gene in advanced prostate cancer.
我们最近从含人染色体区域11p13 - cen的大鼠前列腺癌细胞中分离出KAI1基因,它是一种前列腺癌转移抑制基因。本研究旨在进一步确定KAI1基因在11号染色体短臂上的区域,并检测该区域在人类前列腺癌进展过程中的缺失是否具有显著性。
利用微细胞介导的染色体转移技术,将人11号染色体的一小部分(即11p13 - cen)重新导入高转移性大鼠前列腺癌细胞中。在人类前列腺癌组织中检测人11号染色体上多态性微卫星位点的杂合性缺失(LOH)。
包含KAI1基因的人11号染色体最小区域位于11p11.2的近端区域,由D11S554位点划分。在死于转移性前列腺癌的尸检病例的转移组织中,位于与KAI1位点相同区域的D11S1344位点的LOH或等位基因不平衡百分比为70%(10例信息性病例中的7例),而在同一病例的原发性肿瘤以及临床局限性前列腺癌病例中的百分比分别为33%(9例信息性病例中的3例)和8%(12例信息性病例中的1例)。
这些发现表明,在晚期前列腺癌中,包含KAI1基因的11p着丝粒区域存在高频率的LOH或等位基因不平衡。