SUPPRESSION OF MALIGNANT PHENOTYPE IN A HUMAN PROSTATE-CANCER CELL-LINE BY FRAGMENTS OF NORMAL CHROMOSOMAL REGION 17Q

Recent evidence obtained by in situ hybridization indicates that chrom osomal region 17q is often lost in prostate tumors, To substantiate th e presence of tumor suppressor genes in this chromosomal region, norma l human 17q tagged with a neomycin resistance gene was transferred int o a human prostate cancer cell line, PPC-I, by microcell-mediated chro mosome transfer, Two hybrid clones were obtained, both of which shelve d decreased tumorigenicity in athymic nude mice and decreased efficien cy of colony formation in soft agar with respect to PPC-1. When microc ells were irradiated prior to transfer of chromosomal region 17q to de termine which subchromosomal regions carry the potential tumor suppres sor gene(s), 10 hybrid clones were obtained, including 6 fully maligna nt and 4 suppressed clones, Analysis of polymorphic loci on 17q in the series of hybrid clones suggested that a tumor suppressor gene associ ated with prostate cancer was located in a region no more than 28 cM l ong at 17q12-q22, which includes the BRCA1 gene involved in hereditary breast cancer.