Leigh D A, Ferguson V, Bentel J M, Miller J O, Smith G J
Carcinogenesis Research Unit, School of Pathology, University of New South Wales, Kensington, Australia.
Mol Carcinog. 1990;3(6):387-92. doi: 10.1002/mc.2940030611.
An in vitro cell model of mouse lung alveologenic carcinoma consisting of preneoplastic nonmalignant cells, spontaneously transformed cells, and urethane-induced malignant cells was analyzed for phenotypic and genotypic changes associated with the transition to neoplasia. The polymerase chain reaction (PCR) was used to amplify the cDNA derived from the c-Ki-ras mRNA corresponding to exons 1 and 2 of the proto-oncogene. This approach allowed analysis of the gene transcription product rather than potentially unexpressed DNA. Direct sequencing of the PCR product identified a common single point mutation, alone or together with wild-type mRNA for c-Ki-ras, in all of the malignant clones. An A----G transition in the second base position of codon 61 was common to spontaneously malignant and chemical tumor-derived cell lines and to lines selected for lung metastatic behavior. The absence of the mutation in the nonmalignant cells suggests that the Ki-ras mutation may be a factor in onset or maintenance of the malignant phenotype and, at least in vitro, may be a late event in the transformation process.
