ras oncogene activation in mammary carcinomas induced by N-methyl-N-nitrosourea in Copenhagen rats.
The occurrence of Ha-ras and Ki-ras oncogenes was investigated in mammary tumors produced by treating genetically resistant Copenhagen (Cop) rats with N-methyl-N-nitrosourea. G35-->A codon 12 mutations in both Ha-ras and Ki-ras genes were analyzed by a polymerase chain reaction/liquid hybridization and gel retardation assay. More than half of the adenocarcinomas analyzed contained an activated Ha-ras gene. This was also the predominant mutation in similar tumors from susceptible Buf/N rats, suggesting a common mechanism of initiation. In contrast, only two of 15 mammary adenosquamous carcinomas from the Cop rats contained an activated Ha-ras gene, suggesting a different initiation mechanism for most of these tumors. Ki-ras activation was found in none of five and one of five adenocarcinomas from Buf/N and Cop rats, respectively, and in none of 13 adenosquamous carcinomas from Cop rats. These results suggest that Ki-ras activation does not play a major role in the initiation of the mammary tumors.
Lu
S J
SJ
Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Archer
M C
MC
D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D008770:Methylnitrosourea; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D051381:Rats; D011915:Rats, Inbred BUF; D011919:Rats, Inbred Strains
D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D008770:Methylnitrosourea