Functional evidence for the presence of tumor suppressor gene on chromosome 10p15 in human prostate cancers

Loss of heterozygosity on chromosome 10p was observed frequently in human p rostate cancers. Studies have demonstrated that the introduction of the sho rt arm of human chromosome 10 into a human prostate cancer cell line, PPC-I , by microcell-mediated chromosome transfer (MMCT), suppressed the malignan t phenotype, suggesting the presence of a prostate tumor suppressor gene(s) within a region of 17 cM at distal 10p, To narrow down the candidate regio n harboring the tumor suppressor gene, a series of 10p fragments were trans ferred into PPC-1 cells by MMCT using a panel of hamster-human hybrid cells containing various portions of 10p, Pour of the six hybrid tells obtained showed decreased tumorigenicity when injected subcutaneously irate athymic nude mice. Tumors developed only at six of 40 injection sites for these fou r hybrid cells. In contrast, the other two hybrid cells, as well as parenta l PPC-1 cells, were judged to he fully tumorigenic because tumors appeared at a total 26 of 32 sites for the two hybrid cells and 15 of 16 sites for P PC-I, Allelotyping of 10p combined with fluorescence in situ hybridization in these hybrid cells suggested that a prostate tumor suppressor gene was l ocated within a fragment of approximately 1.2 Mb flanked by D10S1172 and D1 0S226 on 10p15.1.