This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blackburn, A. C. Articles by Jerry, D. J. Search for Related Content PubMed PubMed Citation Articles by Blackburn, A. C. Articles by Jerry, D. J.

BALB/c Alleles for Prkdc and Cdkn2a Interact to Modify Tumor Susceptibility in Trp53+/- Mice¹

Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts 01003 [A. C. B., J. S. B., D. J. J.]; Department of Pathology, Baystate Medical Center, Springfield, Massachusetts 01199 [S. P. N., C. N. O.]; and Statistical Consulting Unit, Australian National University, Canberra ACT 2601, Australia [J. T. W.]

In mice heterozygous for p53 (Trp53^+/-), the incidence of mammary tumors varies among strains, with C57BL/6 being resistant and BALB/c being susceptible. Mammary tumor phenotypes were examined in female Trp53^+/- F1 mice (C57BL/6 x BALB/c;n = 19) and N2 backcross mice [(C57BL/6 x BALB/c) x BALB/c] (n = 224). Susceptibility to mammary tumors segregated as a dominant phenotype in F1 females, but a higher frequency and shorter latency in N2 mice indicated a contribution from recessive-acting modifiers. Segregation of the hypomorphic BALB/c alleles for DNA-dependent protein kinase catalytic subunit (Prkdc) and p16^INK4A (Cdkn2a) was analyzed in the N2 mice. The time to first tumor (considering all tumor types) was significantly different among the four genotype combinations (P = 0.01). Cdkn2a had a strong effect (P = 0.008) but was restricted to Prkdc^B/B mice (P = 0.001), indicating a strong interaction between the loci. Differences in mammary tumor occurrence among genotypes for Prkdc and Cdkn2a in N2 mice were not statistically significant. This study indicates that BALB/c Prkdc and Cdkn2a alleles do modify tumor incidence in Trp53^+/- mice and highlights the complexity of gene interaction effects in determining cancer phenotypes but discounts these alleles as major recessive loci contributing to spontaneous mammary tumor susceptibility.

This article has been cited by other articles:

				A. C. Blackburn, L. Z. Hill, A. L. Roberts, J. Wang, D. Aud, J. Jung, T. Nikolcheva, J. Allard, G. Peltz, C. N. Otis, et al. Genetic Mapping in Mice Identifies DMBT1 as a Candidate Modifier of Mammary Tumors and Breast Cancer Risk Am. J. Pathol., June 1, 2007; 170(6): 2030 - 2041. [Abstract] [Full Text] [PDF]

				A. C. Blackburn, S. C. McLary, R. Naeem, J. Luszcz, D. W. Stockton, L. A. Donehower, M. Mohammed, J. B. Mailhes, T. Soferr, S. P. Naber, et al. Loss of Heterozygosity Occurs via Mitotic Recombination in Trp53+/- Mice and Associates with Mammary Tumor Susceptibility of the BALB/c Strain Cancer Res., August 1, 2004; 64(15): 5140 - 5147. [Abstract] [Full Text] [PDF]

				C.-M. Chen and R. R. Behringer Ovca1 regulates cell proliferation, embryonic development, and tumorigenesis Genes & Dev., February 1, 2004; 18(3): 320 - 332. [Abstract] [Full Text] [PDF]

				K. Felix, A. Polack, W. Pretsch, S. H. Jackson, L. Feigenbaum, G.-W. Bornkamm, and S. Janz Moderate Hypermutability of a Transgenic lacZ Reporter Gene in Myc-Dependent Inflammation-Induced Plasma Cell Tumors in Mice Cancer Res., January 15, 2004; 64(2): 530 - 537. [Abstract] [Full Text] [PDF]