Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk
dc.contributor.author | Blackburn, Anneke | |
dc.contributor.author | Hill, Linda Z. | |
dc.contributor.author | Roberts, Amy L. | |
dc.contributor.author | Wang, Jun | |
dc.contributor.author | Aud, Dee | |
dc.contributor.author | Jung, Jimmy | |
dc.contributor.author | Nikolcheva, Tania | |
dc.contributor.author | Allard, John | |
dc.contributor.author | Peltz, Gary | |
dc.contributor.author | Otis, Christopher | |
dc.contributor.author | Cao, Qing | |
dc.contributor.author | Ricketts, Reva St. J. | |
dc.contributor.author | Naber, Stephen P | |
dc.contributor.author | Mollenhauer, Jan | |
dc.contributor.author | Poustka, A | |
dc.contributor.author | Malamud, Daniel | |
dc.contributor.author | Jerry, Joseph | |
dc.date.accessioned | 2015-12-07T22:16:24Z | |
dc.date.issued | 2007 | |
dc.date.updated | 2015-12-07T07:51:16Z | |
dc.description.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 ∼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 significandy 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 < 0.0001). These experiments demonstrate the use of Trp53+/- mice as a sensitized background to screen for low-penetrance modifiers of cancer. The results identify a novel mammary tumor susceptibility locus in mice and support a role for DMBT1 in suppression of mammary tumors in both mice and women. | |
dc.identifier.issn | 0002-9440 | |
dc.identifier.uri | http://hdl.handle.net/1885/18019 | |
dc.publisher | American Society for Investigative Pathology | |
dc.source | American Journal of Pathology | |
dc.subject | Keywords: protein dmbt1; tumor suppressor protein; unclassified drug; Dmbt1 protein, mouse; mucin; protein p53; allele; animal model; article; breast cancer; cancer risk; cancer susceptibility; chromosome 7; controlled study; female; gene mapping; genetic screening | |
dc.title | Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk | |
dc.type | Journal article | |
local.bibliographicCitation.issue | 6 | |
local.bibliographicCitation.lastpage | 2041 | |
local.bibliographicCitation.startpage | 2030 | |
local.contributor.affiliation | Blackburn, Anneke, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Hill, Linda Z., University of Massachusetts | |
local.contributor.affiliation | Roberts, Amy L., University of Massachusetts | |
local.contributor.affiliation | Wang, Jun, Roche Palo Alto | |
local.contributor.affiliation | Aud, Dee, Roche Palo Alto | |
local.contributor.affiliation | Jung, Jimmy, Roche Palo Alto | |
local.contributor.affiliation | Nikolcheva, Tania, Roche Palo Alto | |
local.contributor.affiliation | Allard, John, Roche Palo Alto | |
local.contributor.affiliation | Peltz, Gary, Roche Palo Alto | |
local.contributor.affiliation | Otis, Christopher, University of Massachusetts | |
local.contributor.affiliation | Cao, Qing, Baystate Medical Center | |
local.contributor.affiliation | Ricketts, Reva St. J., Baystate Medical Center | |
local.contributor.affiliation | Naber, Stephen P, Baystate Medical Center | |
local.contributor.affiliation | Mollenhauer, Jan, Molecular Genome Analysis | |
local.contributor.affiliation | Poustka, A, German Cancer Research Center | |
local.contributor.affiliation | Malamud, Daniel, New York University | |
local.contributor.affiliation | Jerry, Joseph, University of Massachusetts | |
local.contributor.authoremail | u4048450@anu.edu.au | |
local.contributor.authoruid | Blackburn, Anneke, u4048450 | |
local.description.embargo | 2037-12-31 | |
local.description.notes | Imported from ARIES | |
local.identifier.absfor | 111203 - Cancer Genetics | |
local.identifier.ariespublication | u4133361xPUB3 | |
local.identifier.citationvolume | 170 | |
local.identifier.doi | 10.2353/ajpath.2007.060512 | |
local.identifier.scopusID | 2-s2.0-34447295401 | |
local.identifier.uidSubmittedBy | u4133361 | |
local.type.status | Published Version |
Downloads
Original bundle
1 - 1 of 1
Loading...
- Name:
- 01_Blackburn_Genetic_mapping_in_mice_2007.pdf
- Size:
- 811.94 KB
- Format:
- Adobe Portable Document Format