Kao C, Wu S Q, Bhatthacharya M, Meisner L F, Reznikoff C A
Department of Biochemistry, University of Wisconsin, Madison 53792.
Genes Chromosomes Cancer. 1992 Mar;4(2):158-68. doi: 10.1002/gcc.2870040210.
Five independent clones of Simian virus 40 (SV40)-immortalized human uroepithelial cells (CK/SV-HUC) were established after transfection of HUC cultures from the same tissue donor with plasmids encoding SV40 large T and small t antigen genes. Each CK/SV-HUC clone contained a unique SV40 integration site, and all expressed similar levels of SV40 mRNA. All five clones were nontumorigenic, but clones 2, 4, and 5 tumorigenically transformed after transfection at P19 with mutant EJ/ras and also spontaneously after 40 serial passages in vitro. In contrast, CK/SV-HUC clones 1 and 3 did not transform when either approach was used. These differences in transformability among CK/SV-HUC clones could not be predicted based on differences in SV40 gene expression nor on any in vitro growth property tested. In cytogenetic analyses, a transformable clone showed losses of three chromosome arms containing putative cancer suppressor gene regions, including 3p14----pter, 13q, and 11p, whereas the nontransformable clones showed none of these losses. Thus these data indicate that genetic losses on 3p, 11p, and 13q may contribute to tumorigenic transformation of SV40-immortalized human uroepithelial cells.
用编码猿猴病毒40（SV40）大T抗原和小t抗原基因的质粒转染来自同一组织供体的人尿路上皮细胞（HUC）培养物后，建立了5个独立的SV40永生化人尿路上皮细胞克隆（CK/SV-HUC）。每个CK/SV-HUC克隆都含有一个独特的SV40整合位点，并且都表达相似水平的SV40 mRNA。所有5个克隆都无致瘤性，但克隆2、4和5在P19时用突变型EJ/ras转染后发生致瘤性转化，并且在体外连续传代40次后也自发发生转化。相比之下，使用任何一种方法时，CK/SV-HUC克隆1和3都没有发生转化。基于SV40基因表达的差异或所测试的任何体外生长特性，无法预测CK/SV-HUC克隆之间在转化能力上的这些差异。在细胞遗传学分析中，一个可转化的克隆显示出包含假定抑癌基因区域的三条染色体臂缺失，包括3p14----pter、13q和11p，而非可转化的克隆则没有这些缺失。因此，这些数据表明3p、11p和13q上的基因缺失可能有助于SV40永生化人尿路上皮细胞的致瘤性转化。
