Miyamoto S, Guzman R C, Shiurba R A, Firestone G L, Nandi S
Cancer Research Laboratory, University of California, Berkeley 94720.
Cancer Res. 1990 Sep 15;50(18):6010-4.
ras protooncogenes activated by a point mutation have been implicated in the initiation of mammary carcinogenesis. However, the nature of phenotypic alterations induced by activated ras protoonocogenes during initiation has not been well understood. In the present studies, the phenotypic manifestation of activated ras genes was directly analyzed by transfecting them into normal mouse mammary epithelial cells. The ras genes were cotransfected with pSV2neo which expresses the bacterial neomycin resistance gene to partially select for successful transfectants in culture. Transfection of activated Ha-ras protooncogenes, containing a point mutation in codon 12, caused hyperplasia in the mouse mammary gland following transplantation. Hyperplastic phenotype is a prerequisite for neoplastic development. The hyperplasias induced by the activated Ha-ras protooncogenes, however, were not immortal in vivo, another essential characteristic of preneoplastic and neoplastic mouse mammary cells. Control cells transfected only with pSV2neo did not produce any hyperplasia. These results suggest that a functional role of activated ras protooncogenes in the initiation of mouse mammary carcinogenesis may be the induction of a hyperplastic phenotype, a prelude to neoplastic development.
由点突变激活的ras原癌基因与乳腺癌发生的起始有关。然而，在起始阶段由激活的ras原癌基因诱导的表型改变的本质尚未得到很好的理解。在本研究中，通过将激活的ras基因转染到正常小鼠乳腺上皮细胞中来直接分析其表型表现。ras基因与表达细菌新霉素抗性基因的pSV2neo共转染，以便在培养中部分选择成功的转染子。转染含有密码子12点突变的激活的Ha-ras原癌基因后，移植到小鼠乳腺中会导致增生。增生表型是肿瘤发生发展的一个先决条件。然而，由激活的Ha-ras原癌基因诱导的增生在体内并不是永生的，这是肿瘤前和肿瘤小鼠乳腺细胞的另一个重要特征。仅用pSV2neo转染的对照细胞未产生任何增生。这些结果表明，激活的ras原癌基因在小鼠乳腺癌发生起始中的功能作用可能是诱导增生表型，这是肿瘤发生发展的前奏。
