A retrovirus that expresses v-abl and c-myc oncogenes rapidly induces plasmacytomas.
ABL-MYC, a murine retrovirus that encodes the v-abl and c-myc oncogenes, was constructed from Abelson murine leukemia virus (A-MuLV) in order to assess the biological consequences of co-expression of these genes in lymphoid cells. When inoculated into mice this retrovirus induced plasmacytomas in up to 100% of infected mice and less frequently induced pre-B lymphomas. Both tumor types contained genome-length proviruses in one or a few chromosomal locations, were mono- or oligoclonal as judged by immunoglobulin gene rearrangement and had unrearranged endogenous c-myc loci. The type of tumor induced depended upon the age and strain of mouse, and whether helper virus was present in the inoculated virus pool. ABL-MYC induced plasmacytomas with or without helper virus, with or without pretreatment of the mice with pristane, and in strains of mice resistant to pristane-induced plasmacytomas. Pristane treatment prior to ABL-MYC infection shortened the latent period of plasmacytomagenesis and produced mostly IgM-secreting tumors rather than IgA-secreting tumors, which predominantly arose in the absence of pristane. Control viruses for ABL-MYC with either a deletion in v-abl or a frameshift mutation in c-myc caused predominantly monocyte/macrophage tumors and pre-B-cell lymphomas respectively. Histopathological analysis of ABL-MYC-infected mice showed foci of transformed plasma cells as early as 14 days after infection. These results indicate that v-abl and c-myc act synergistically to transform mature B cells with high efficiency.
Largaespada
D A
DA
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
Kaehler
D A
DA
Mishak
H
H
Weissinger
E
E
Potter
M
M
Mushinski
J F
JF
Risser
R
R
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D015870:Gene Expression; D016313:Genes, abl; D016259:Genes, myc; D005822:Genetic Vectors; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D016374:Oncogene Proteins v-abl / Q000235:genetics*; D010954:Plasmacytoma / Q000235:genetics* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012190:Retroviridae
D004273:DNA, Neoplasm; D016374:Oncogene Proteins v-abl; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger