Histogenesis and clonality of pancreatic tumors induced by v-myc and v-raf oncogenes in NFS/N mice.
Newborn NFS/N mice were inoculated with pseudotypes of murine retroviruses containing murine v-raf, avian v-myc, or both v-raf and v-myc within a single construct. Foci of dysplastic acinar cells, similar to those observed in rats given chemical carcinogens, were induced in 77% of mice inoculated with the raf/myc construct with a latency as short as 15 days. However, all animals given this construct also developed fibrosarcomas, erythroblastosis, and lymphomas and died within 70 days of infection, before pancreatic acinar carcinomas developed. Dysplastic foci were also observed in mice infected with viruses containing v-raf or v-myc alone with latencies of 3-4 weeks, and carcinomas were seen after an average latency of 150 days in 31% of mice infected with either of two viruses expressing v-myc alone. Two primary carcinomas were transplanted in mice, and in vitro cell lines were developed from one of the transplants. DNA prepared from seven primary carcinomas, the two transplanted tumors, and the in vitro cell lines was hybridized with a v-myc probe. Each tumor had a unique pattern of proviral integrations that was retained, with the gain or loss of single sites, in the transplants and derivative cell lines. The clonal nature of the advanced pancreatic acinar carcinomas is discussed in relation to their histogenesis and the transforming potentials of the raf and myc oncogenes.
Fredrickson
T N
TN
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Hartley
J W
JW
Wolford
N K
NK
Resau
J H
JH
Rapp
U R
UR
Morse
H C
HC
D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D004247:DNA / Q000032:analysis; D005814:Genes, Viral; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009857:Oncogenes; D010190:Pancreatic Neoplasms / Q000032:analysis / Q000235:genetics* / Q000473:pathology; D012190:Retroviridae / Q000235:genetics; D014407:Tumor Cells, Cultured
D004247:DNA