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Activated Ki-ras proto-oncogene in spontaneously transformed and chemical tumor-derived cell lines related to the mouse lung alveologenic carcinoma

✍ Scribed by Don A. Leigh; Vicki Ferguson; Jacqueline M. Bentel; Juliet O. Miller; Garry J. Smith


Publisher
John Wiley and Sons
Year
1990
Tongue
English
Weight
584 KB
Volume
3
Category
Article
ISSN
0899-1987

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✦ Synopsis


Abstract

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.