v-myc and v-raf act synergistically to induce B-cell tumors in pristane-primed adult BALBC mice.
In a variety of systems, evidence is accumulating which suggests that neoplastic transformation requires the action of two or more genes such as mutated or over-expressed proto-oncogenes. To determine whether the cytoplasmic serine/threonine kinase oncogene raf could complement a deregulated myc gene and induce tumors in adult mice, BALBC mice were primed with an intraperitoneal (ip.) injection of mineral oil (pristane) and then given an ip. injection of a retroviral construct, J1, J2 or J5, which expresses either v-raf (J1), v-myc (J5) or both (J2). The J1 virus induced no tumors in 150 days in 38 mice, except for 5 helper virus-associated T-cell lymphomas. Under identical conditions the J5 virus, which expresses only v-myc, induced exclusively monocytic neoplasms in 93% of 15 mice. The J2 virus expresses both v-myc and v-raf and caused equal numbers of monocytic and B cell tumors in 66% of 30 mice. Under these conditions, it appears that v-raf expression acts synergistically with v-myc to induce the transformation of B cells, which neither oncogene could do alone. The J3 virus, which originally contained a complete v-myc and an inactivated v-raf, can induce tumors of later stage B cells (plasmacytomas, Potter et al., 1987). Recent studies of virus recovered from these plasmacytomas (called the J3V1 virus, Troppmair et al., 1989) show that the J3 virus has undergone deletions which have reactivated v-raf in a mutated form. Only J3V1, not J3, induced tumors in vivo. Our data presented here corroborate Troppmair et al. and extend Potter et al. (1987) which reported that J3 (presumably J3V1) induced 10% myeloid tumors and 90% plasmacytomas. In light of the discovery, our J2 and J3 data indicate that in combination with the same form of v-myc, different forms of v-raf induce different spectra of tumors.
Kurie
J M
JM
Laboratory of Genetics, National Cancer Institute, Bethesda, Maryland 20892.
Morse
H C
HC
Principato
M A
MA
Wax
J S
JS
Troppmair
J
J
Rapp
U R
UR
Potter
M
M
Mushinski
J F
JF
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D015152:Blotting, Northern; D015139:Blotting, Southern; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015321:Gene Rearrangement; D008223:Lymphoma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D016274:Oncogene Protein p55(v-myc); D027384:Oncogene Proteins v-raf; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011519:Proto-Oncogenes; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D012190:Retroviridae / Q000235:genetics*; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D013729:Terpenes
D002273:Carcinogens; D004273:DNA, Neoplasm; D016274:Oncogene Protein p55(v-myc); D012334:RNA, Neoplasm; D015682:Retroviridae Proteins, Oncogenic; D013729:Terpenes; C009042:pristane; D011505:Protein-Tyrosine Kinases; D027384:Oncogene Proteins v-raf