Harper J R, Reynolds S H, Greenhalgh D A, Strickland J E, Lacal J C, Yuspa S H
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD.
Carcinogenesis. 1987 Dec;8(12):1821-5. doi: 10.1093/carcin/8.12.1821.
Mouse skin papillomas and squamous cell carcinomas induced by initiation with 7,12-dimethylbenz[a]anthracene and promotion with phorbol esters, such as 12-O-tetradecanoyl phorbol-13-acetate, frequently contain an activated Harvey ras gene. Six murine epidermal cells lines established from pooled skin papillomas previously tested negative in the NIH-3T3 assay, but have an altered differentiation program by a variety of criteria. The Harvey ras gene and its p21 protein product from these cell lines have been analyzed for alterations responsible for their altered growth and differentiation properties that were undetectable by 3T3 transfection assays. In comparison with primary papillomas and carcinomas, shown to have a point mutation in codon 61 of the Harvey ras gene, resulting in a p21 product with the diagnostic alteration in SDS-PAGE, the papilloma cell lines exhibited neither the codon 61 mutation, nor p21 product with altered migration in SDS-PAGE. These findings suggest that these papilloma cell lines contain a genetic lesion(s), other than Harvey ras activation, that may be responsible for their altered epithelial differentiation patterns and thus may serve as a useful model for identifying lesions involved in malignant conversion.
用7,12 - 二甲基苯并[a]蒽引发、佛波酯（如12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯）促进诱导产生的小鼠皮肤乳头瘤和鳞状细胞癌，常含有激活的哈维鼠肉瘤病毒癌基因（Harvey ras gene）。从汇集的皮肤乳头瘤中建立的6种小鼠表皮细胞系，先前在NIH - 3T3检测中呈阴性，但根据多种标准其分化程序已发生改变。对这些细胞系中的哈维鼠肉瘤病毒癌基因及其p21蛋白产物进行了分析，以寻找导致其生长和分化特性改变的变异，而这些变异在3T3转染检测中无法检测到。与原发性乳头瘤和癌相比，原发性乳头瘤和癌在哈维鼠肉瘤病毒癌基因的第61密码子处有一个点突变，导致p21产物在SDS - PAGE中有诊断性改变，而乳头瘤细胞系既没有第61密码子突变，也没有在SDS - PAGE中迁移改变的p21产物。这些发现表明，这些乳头瘤细胞系含有除哈维鼠肉瘤病毒癌基因激活之外的遗传损伤，这可能是其上皮分化模式改变的原因，因此可能作为识别参与恶性转化的损伤的有用模型。
