Murine retrovirus, 3611 MSV, harboring the transduced raf oncogene induces fibrosarcoma in newborn mice. A construct carrying both raf and the avian oncogene, myc (pHWJ-2), induces hematopoetic neoplasms consisting of immunoblastic lymphomas of both T and B lineage cells and erythroblastosis in addition to less prominent fibrosarcomas and adenocarcinoma less than 3 weeks after inoculation. Constructs carrying only the myc oncogene induce tumors after a latency of equal to or greater than 9 weeks. A variant of the myc only virus, J-3, was found to induce altered foci in cultured fibroblast cells. Neonatal mice develop carcinoma in pancreas, liver and lung when inoculated with this variant, with a latency of 2 to 6 months. The raf oncogene induced transformation of hematopoetic and epithelial cells and is enhanced by the presence of the myc gene which apparently does not transform these cells when grown in standard culture media. Thus, simultaneous expression of both raf and myc oncogenes in these cells alters their respective transforming spectra. Southern blot analysis on the DNA from J-3 (myc only) - induced tumors, as well as from cell lines established from these tumors, showed that at least three out of four tumors are clonal in nature, that in one instance part of the viral sequences were deleted, and in another a repair of the nonfunctional v-raf gene in the virus seems to have occurred. In parallel with these results, we detected, by Northern hybridization, that the genomic RNA transcripts of these two viruses, J-3 and J-3* also differ in size as though the deleted v-raf gene in J-3 had been repaired by recombination with the cellular raf-1 gene.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005419-01
Application #
4692439
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code