| Title | Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk. |
| Publication Type | Journal Article |
| Year of Publication | 2007 |
| Authors | Blackburn, AC, Hill, LZ, Roberts, AL, Wang, J, Aud, D, Jung, J, Nikolcheva, T, Allard, J, Peltz, G, Otis, CN, Cao, QJ, Ricketts, RSt J, Naber, SP, Mollenhauer, J, Poustka, A, Malamud, D, D Jerry, J |
| Journal | The American journal of pathology |
| Volume | 170 |
| Issue | 6 |
| Pagination | 2030-41 |
| Date Published | 2007 Jun |
| Abstract | Low-penetrance breast cancer susceptibility alleles seem to play a significant role in breast cancer risk but are difficult to identify in human cohorts. A genetic screen of 176 N2 backcross progeny of two Trp53(+/-) strains, BALB/c and C57BL/6, which differ in their susceptibility to mammary tumors, identified a modifier of mammary tumor susceptibility in an approximately 25-Mb interval on mouse chromosome 7 (designated SuprMam1). Relative to heterozygotes, homozygosity for BALB/c alleles of SuprMam1 significantly decreased mammary tumor latency from 70.7 to 61.1 weeks and increased risk twofold (P = 0.002). Dmbt1 (deleted in malignant brain tumors 1) was identified as a candidate modifier gene within the SuprMam1 interval because it was differentially expressed in mammary tissues from BALB/c-Trp53(+/-) and C57BL/6-Trp53(+/-) mice. Dmbt1 mRNA and protein was reduced in mammary glands of the susceptible BALB/c mice. Immunohistochemical staining demonstrated that DMBT1 protein expression was also significantly reduced in normal breast tissue from women with breast cancer (staining score, 1.8; n = 46) compared with cancer-free controls (staining score, 3.9; n = 53; P |
| Alternate Journal | Am. J. Pathol. |
Veterinary and Animal Sciences