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 chromosomal region 17q is often lost in prostate tumors, To substantiate the presence of tumor suppressor genes in this chromosomal region, normal human 17q tagged with a neomycin resistance gene was transferred into a human prostate cancer cell line, PPC-I, by microcell-mediated chromosome transfer, Two hybrid clones were obtained, both of which shelved decreased tumorigenicity in athymic nude mice and decreased efficiency of colony formation in soft agar with respect to PPC-1. When microcells were irradiated prior to transfer of chromosomal region 17q to determine which subchromosomal regions carry the potential tumor suppressor gene(s), 10 hybrid clones were obtained, including 6 fully malignant and 4 suppressed clones, Analysis of polymorphic loci on 17q in the series of hybrid clones suggested that a tumor suppressor gene associated with prostate cancer was located in a region no more than 28 cM long at 17q12-q22, which includes the BRCA1 gene involved in hereditary breast cancer.