| Mapping of Three Genetic Determinants of Susceptibility to Estrogen-Induced Mammary Cancer within the Emca8 Locus on Rat Chromosome 5. | |
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MedLine Citation:
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PMID: 23151807 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The ACI rat model of 17β-estradiol (E2)-induced mammary cancer has gained wide use in the study of breast cancer etiology, prevention and genetics. Emca8, a QTL that determines susceptibility to E2-induced mammary cancer, was previously mapped to rat chromosome 5 (RNO5) in an intercross between resistant Brown Norway (BN) and susceptible ACI rats. In this study, a panel of congenic rat strains, each of which carries BN alleles across a defined segment of RNO5 on the ACI genetic background, was generated and used to map more precisely the Emca8 determinants of mammary cancer susceptibility. Three distinct genetic determinants were localized within Emca8, and two of these were mapped to intervals of less than 15 megabases. Emca8.1 harbors Cdkn2a, Cdkn2b and other genes and is orthologous to the 9p21 breast cancer locus identified in genome wide and candidate gene association studies. Emca8.2 harbors Cdkn2c and other genes and is orthologous to the 1p32 locus in humans that is frequently deleted in breast cancers. Both Emca8.1 and Emca8.2 harbor copy number variants that are orthologous to copy number variant regions in humans. Gene expression profiles were defined for mammary tissues from E2 treated ACI and ACI.BN-Emca8 rats to define the impact of Emca8 on gene expression and identify differentially expressed genes residing within Emca8.1 and Emca8.2. This study further illustrates the relevance of the ACI rat model of E2-induced mammary cancer for identifying novel genetic determinants of breast cancer susceptibility and defining the mechanisms through which estrogens contribute to breast cancer development. |
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Authors:
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Beverly S Schaffer; Kristin M Leland-Wavrin; Scott G Kurz; John A Colletti; Nicole L Seiler; Christopher L Warren; James D Shull |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-14 |
Journal Detail:
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Title: Cancer prevention research (Philadelphia, Pa.) Volume: - ISSN: 1940-6215 ISO Abbreviation: Cancer Prev Res (Phila) Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101479409 Medline TA: Cancer Prev Res (Phila) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1not currently affiliated, not currently affiliated. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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