High levels of c-myc gene expression precede point mutational activation of Ki-ras in mouse lung cancer.
A cell culture model of mouse lung alveologenic carcinoma, consisting of type 2 pneumocyte-related cells, known to contain an A to G transition in the second base position of codon 61 of the c-Ki-ras gene has been examined for molecular changes affecting nuclear oncogenes. A small, twofold increase in c-myc mRNA levels and transcription levels was observed in malignant cell lines (C4SE9 and NULB5) compared with non-malignant cells (C4E10). Interestingly, the transcriptional level of the c-myc gene in C4E10 cells was very high relative to any other gene examined. Similar high levels of c-myc gene expression levels were also observed in type 2 pneumocytes obtained from normal mouse lung tissue. No major DNA rearrangements or amplifications were detected between C4E10 cells and either C4SE9 or NULB5 cell lines. These data suggest that high levels of c-myc gene expression occurred prior to the activating point mutation of the c-Ki-ras gene and may predispose the type 2 pneumocyte to transformation.
Polly
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Carcinogenesis Research Unit, School of Pathology, University of New South Wales, Sydney, Australia.
Nicholson
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RC
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005784:Gene Amplification / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics; D016259:Genes, myc / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000502:physiology; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D017354:Point Mutation / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic / Q000235:genetics
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D004247:DNA