Moloney murine leukemia virus-induced lymphomas in p53-deficient mice: overlapping pathways in tumor development?

Baxter, E.W., Blyth, K., Donehower, L., Cameron, E.R., Onions, D.E. and Neil, J.C. (1996) Moloney murine leukemia virus-induced lymphomas in p53-deficient mice: overlapping pathways in tumor development? Journal of Virology, 70(4), pp. 2095-100. (PMID:8642629) (PMCID:PMC190045)

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Publisher's URL: http://jvi.asm.org/content/70/4/2095.long

Abstract

The effect of Moloney murine leukemia virus (MoMLV) infection was examined in mice lacking a functional p53 gene. Virus-infected p53-/- mice developed tumors significantly faster than uninfected p53-/- or virus-infected p53+/+ littermates. However, the degree of synergy between MoMLV and the p53 null genotype was weaker than the synergy between either of these and c-myc transgenes. A similar range of T-cell tumor phenotypes was represented in all p53 genotype groups, including p53-/- mice, which developed thymic lymphomas as the most common of several neoplastic diseases. Lack of p53 was associated with higher rates of metastasis and the ready establishment of tumors in tissue culture. Loss of the wild-type allele was a common feature of tumors in p53+/- mice and was complete in tumor cells in vitro, but this appeared to occur by a mechanism other than proviral insertion at the wild-type allele. A lower average MoMLV proviral copy number was observed in tumors of the p53 null and heterozygote groups, suggesting that the absence of a functional p53 gene reduced the number of steps required to complete the malignant phenotype. Mink cell focus-forming virus-like proviruses were detected in tumors of all infected mice but were relatively rare in p53 null mice. Analysis of c-myc, pim-1, and pal-1 showed that these loci were occupied by proviruses in some cases but at similar frequencies in p53 wild-type and null mice. In conclusion, while inactivation of p53 in the germ line predisposes mice to tumors similar in phenotype to those induced by MoMLV, it appears that virus-induced tumors generally occur without p53 loss. We speculate that a bcl-2-like function carried or induced by MoMLV may underlie this p53-independent pathway.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Blyth, Dr Karen and Cameron, Professor Ewan and Neil, Professor James and Onions, Professor David
Authors: Baxter, E.W., Blyth, K., Donehower, L., Cameron, E.R., Onions, D.E., and Neil, J.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1070-6321

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