METASTASIS SUPPRESSOR GENES FOR PROSTATE-CANCER

To examine the role of human chromosomes in the development of metasta tic prostate cancer, we introduced a copy of human chromosomes into hi ghly metastatic Dunning R-3327 rat prostatic cancer cells by microcell -mediated chromosome transfer. Each microcell hybrid clones containing human chromosomes 8, 10, 11, and 17, respectively, showed decreased a bility to metastasize to the lung, without any loss of tumorigenicity. This finding demonstrates that these human chromosomes contain metast asis suppressor genes for prostate cancer. Spontaneous deletion of por tions of human chromosomes was observed in human chromosome 10, 11, an d 17 studies. In the human chromosome 8 study, irradiated microcell-me diated chromosome transfer was performed to enrich chromosomal arm del etions of human chromosome 8. 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 whic h part of human chromosomes contained metastasis suppressor gene(s) fo r prostate cancer. Molecular and cytogenetic analyses of microcell hyb rid clones demonstrated that metastasis suppressor genes on human chro mosomes 8, 10, and 11 were located on 8p23-q12, 10q, 11p13-11.2, respe ctively. Further analyses are proposed to confirm the potentially usef ul advantage of this assay system to identify metastasis suppressor ge ne(s) for prostate cancer. (C) 1996 Wiley-Liss, Inc.