A novel combination of K-ras and myc amplification accompanied by point mutational activation of K-ras in a human lung cancer.
Amplifications of two oncogenes, c-K-ras-2 and c-myc, were found in a human lung giant cell carcinoma (LGCC) Lu-65, which is maintained in nude mice. The extent of c-K-ras-2 and myc amplifications were estimated to be 10- and 8-fold, respectively, by means of the Southern hybridization procedure. In addition, NIH3T3 cells were transformed by transfection of Lu-65 DNA and the transforming gene was identified as c-K-ras-2. c-K-ras-2 genes were cloned from a gene library of Lu-65 and a single point mutation causing a substitution of cysteine for glycine in codon 12 was found by DNA sequencing. It was concluded that the amplification of the c-myc and c-K-ras-2 genes are accompanied by point mutational activation of c-K-ras-2 in the human LGCC Lu-65. This is the first report of multiple gene amplification accompanied by a point mutation of oncogenes in human cancer cells, providing further support for the idea that co-operation of at least two activated cellular oncogenes is required for carcinogenesis.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018288:Carcinoma, Small Cell / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004262:DNA Restriction Enzymes; D005784:Gene Amplification; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D009857:Oncogenes; D014183:Transplantation, Heterologous
D004262:DNA Restriction Enzymes