Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome transfer

To identify the metastasis suppressor genes for prostate cancer. Methods: A copy of human chromosomes was introduced into the highly metastatic Dunnin g R-3327 rat prostate cancer cells by the use of microcell-mediated chromos ome transfer. Relationships between the size of human chromosomes introduce d into microcell hybrid clones and the number of lung metastases produced b y the clones were analyzed to determine which part of human chromosomes con tained the metastasis suppressor gene(s) for prostate cancer. To determine portions of human chromosomes introduced, G-banding chromosomal analysis, f luorescence in sial hybridization analysis, and polymerase chain reaction a nalysis were performed. Results: Each of microcell hybrid clones containing human chromosomes 7, 8, 10, 11, 12, or 17 showed decreased ability to meta stasize to the lung without any loss of tumorigenicity. This demonstrates t hat these human chromosomes contain metastasis suppressor genes for prostat e cancer. Spontaneous deletion of portions of human chromosomes was observe d in the human chromosome ?, 10, Il, 12, and 17 studies. In the human chrom osome 8 study, irradiated microcell-mediated chromosome transfer was perfor med to enrich chromosomal arm deletions of human chromosome 8. Molecular an d cytogenetic analyses of microcell hybrid clones demonstrated that metasta sis suppressor genes on human chromosomes were located on 7q21-22, 7q31.2-3 2, 8p21-12, 10q11-22, 11p13-11.2, 12p11-q13, 12q24-ter, and 17pter-q23. KA1 1 and MKK4/SEK1 were identified as metastasis suppressor genes from 11p11.2 and 17p12, respectively. Conclusion: This assay system is useful to identi fy metastasis suppressor gene (s) for prostate cancer.