Murakami Y S, Brothman A R, Leach R J, White R L
Howard Hughes Medical Institute, University of Utah, Salt Lake City 84112, USA.
Cancer Res. 1995 Aug 1;55(15):3389-94.
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-1, by microcell-mediated chromosome transfer. Two hybrid clones were obtained, both of which showed 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.
最近通过原位杂交获得的证据表明，17q染色体区域在前列腺肿瘤中常常缺失。为了证实该染色体区域中肿瘤抑制基因的存在，通过微细胞介导的染色体转移，将携带新霉素抗性基因的正常人17q染色体转入人前列腺癌细胞系PPC-1中。获得了两个杂交克隆，相对于PPC-1，这两个克隆在无胸腺裸鼠中的致瘤性均降低，并且在软琼脂中的集落形成效率也降低。当在转移17q染色体区域之前对微细胞进行辐照，以确定哪些亚染色体区域携带潜在的肿瘤抑制基因时，获得了10个杂交克隆，其中包括6个完全恶性克隆和4个受抑制克隆。对该系列杂交克隆中17q上多态性位点的分析表明，与前列腺癌相关的肿瘤抑制基因位于17q12-q22上一个长度不超过28 cM的区域，该区域包括与遗传性乳腺癌相关的BRCA1基因。
