Ichikawa T, Hosoki S, Suzuki H, Akakura K, Igarashi T, Furuya Y, Oshimura M, Rinker-Schaeffer C W, Nihei N, Barrett J C, Isaacs J T, Ito H
Department of Urology, Chiba University School of Medicine, Japan.
Asian J Androl. 2000 Sep;2(3):167-71.
To identify the metastasis suppressor genes for prostate cancer.
A copy of human chromosomes was introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediated chromosome transfer. Relationships between the size of human chromosomes introduced into microcell hybrid clones and the number of lung metastases produced by the clones were analyzed to determine which part of human chromosomes contained the metastasis suppressor gene(s) for prostate cancer. To determine portions of human chromosomes introduced, G-banding chromosomal analysis, fluorescence in situ hybridization analysis, and polymerase chain reaction analysis were performed.
Each of microcell hybrid clones containing human chromosomes 7, 8, 10, 11, 12, or 17 showed decreased ability to metastasize to the lung without any loss of tumorigenicity. This demonstrates that these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portions of human chromosomes was observed in the human chromosome 7, 10, 11, 12, and 17 studies. In the human chromosome 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletions of human chromosome 8. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasis suppressor genes on human chromosomes were located on 7q21-22, 7q31.2-32, 8p21-12, 10q11-22, 11p13-11.2, 12p11-q13, 12q24-ter, and 17pter-q23. KAI1 and MKK4/SEKI were identified as metastasis suppressor genes from 11p11.2 and 17p12, respectively.
This assay system is useful to identify metastasis suppressor gene (s) for prostate cancer.
鉴定前列腺癌的转移抑制基因。
通过微细胞介导的染色体转移，将一条人类染色体导入高转移性的Dunning R-3327大鼠前列腺癌细胞中。分析导入微细胞杂交克隆的人类染色体大小与克隆产生的肺转移灶数量之间的关系，以确定人类染色体的哪一部分包含前列腺癌的转移抑制基因。为了确定导入的人类染色体部分，进行了G显带染色体分析、荧光原位杂交分析和聚合酶链反应分析。
含有人类染色体7、8、10、11、12或17的每个微细胞杂交克隆转移至肺的能力均下降，而成瘤性未丧失。这表明这些人类染色体包含前列腺癌的转移抑制基因。在对人类染色体7、10、11、12和17的研究中，观察到人类染色体部分的自发缺失。在对人类染色体8的研究中，进行了辐射微细胞介导的染色体转移以富集人类染色体8的染色体臂缺失。对微细胞杂交克隆的分子和细胞遗传学分析表明，人类染色体上的转移抑制基因位于7q21-22、7q31.2-32、8p21-12、10q11-22、11p13-11.2、12p11-q13、12q24-末端和17p末端-q23。分别从11p11.2和17p12鉴定出KAI1和MKK4/SEKI为转移抑制基因。
该检测系统有助于鉴定前列腺癌的转移抑制基因。
