Mammary tumor modifiers in BALB/cJ mice heterozygous for p53 |
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| Authors: | Joanna G Koch Xiangjun Gu Younghun Han Adel K El-Naggar Melissa V Olson Daniel Medina D Joseph Jerry Anneke C Blackburn Gary Peltz Christopher I Amos Guillermina Lozano |
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| Institution: | (1) The University of Texas Graduate School of Biomedical Sciences and the Department of Cancer Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA;(2) Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA;(3) Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA;(4) Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA;(5) Department of Veterinary and Animal Sciences, Molecular and Cellular Biology Program, University of Massachusetts, Amherst, Massachusetts 01003, USA;(6) Pioneer Valley Life Sciences Institute, Springfield, Massachusetts 01199, USA;(7) Roche Palo Alto, Palo Alto, California 94304, USA;(8) Department of Cancer Genetics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe, Box 1010, Houston, TX 77030, USA;(9) Present address: John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia |
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| Abstract: | BALB/c mice are predisposed to developing spontaneous mammary tumors, which are further increased in a p53 heterozygous state. C57BL/6J mice are resistant to induced mammary tumors and develop less than 1% mammary tumors in both
wild-type and p53
+/− states. To map modifiers of mammary tumorigenesis, we have established F1 and F2 crosses and backcrosses to BALB/cJ (N2-BALB/cJ) and C57BL/6J (N2-C57BL/6J) strains. All cohorts developed mammary carcinomas
in p53
+/− females, suggesting that multiple loci dominantly and recessively contributed to mammary tumorigenesis. We mapped two modifiers
of mammary tumorigenesis in the BALB/cJ strain. Mtsm1 (mammary tumor susceptibility modifier), a dominant-acting modifier, is located on chromosome 7. Mtsm1 is suggestive for linkage to mammary tumorigenesis (p = 0.001). We have analyzed the Mtsm1 region to locate candidate genes by comparing it to a rat modifier region, Mcs3, which shares syntenic conservation with Mtsm1. Expression data and SNPs were also taken into account. Five potential candidate genes within Mtsm1 are Aldh1a3, Chd2, Nipa2, Pcsk6, and Tubgcp5. The second modifier mapped is Mtsm2, a recessive-acting modifier. Mtsm2 is located on chromosome X and is significantly linked to mammary tumorigenesis (p = 1.03 × 10−7).
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users. |
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