The Harvey ras 1 gene is activated in papillomavirus-associated carcinomas of the upper alimentary canal in cattle.
The possible activation of ras sequences in papillomavirus-associated carcinomas of the upper alimentary canal of cattle was investigated by restriction enzyme and hybridization analysis, and by DNA-mediated transformation of NIH3T3 cells. In three cancers, a squamous cell carcinoma of the palate, a squamous cell carcinoma of the rumen, and a transitional cell carcinoma of the urinary bladder, repetitive DNA sequences present in the Ha-ras 1 locus showed anomalous restriction patterns, indicating rearrangements and, in the case of the palate cancer, amplification. Genomic DNA from several cancers was capable of inducing focus formation in the NIH3T3 transformation test. DNA from primary, secondary and tertiary transformants was analysed by hybridization to bovine ras probes and by nucleotide sequencing of polymerase chain reaction products. Bovine Ha-ras 1 sequences were found in all transformants, but no nucleotide differences were detected in exon 1 or exon 2 between normal, cancer and transformed cells. It is concluded that the Ha-ras 1 gene is activated in alimentary canal carcinomas, although the activating mutation has not yet been mapped. The possible relationship between papillomavirus infection and activation of the ras gene is considered.
Campo
M S
MS
Beatson Institute for Cancer Research, Bearsden, Glasgow, UK.
McCaffery
R E
RE
Doherty
I
I
Kennedy
I M
IM
Jarrett
W F
WF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000382:microbiology / Q000662:veterinary*; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics* / Q000382:microbiology; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004067:Digestive System Neoplasms / Q000235:genetics / Q000382:microbiology / Q000662:veterinary*; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D011905:Genes, ras; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D015345:Oligonucleotide Probes; D027383:Papillomaviridae / Q000235:genetics* / Q000472:pathogenicity; D016133:Polymerase Chain Reaction; D014162:Transfection
D004273:DNA, Neoplasm; D004279:DNA, Viral; D015345:Oligonucleotide Probes