Document Detail


Mapping of three genetic determinants of susceptibility to estrogen-induced mammary cancer within the Emca8 locus on rat chromosome 5.
MedLine Citation:
PMID:  23151807     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. Cancer Prev Res; 6(1); 59-69. ©2012 AACR.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-14
Journal Detail:
Title:  Cancer prevention research (Philadelphia, Pa.)     Volume:  6     ISSN:  1940-6215     ISO Abbreviation:  Cancer Prev Res (Phila)     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-06-24     Revised Date:  2014-03-20    
Medline Journal Info:
Nlm Unique ID:  101479409     Medline TA:  Cancer Prev Res (Phila)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  59-69     Citation Subset:  IM    
Copyright Information:
©2012 AACR.
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MeSH Terms
Descriptor/Qualifier:
Alleles
Animals
Animals, Congenic
Chromosome Mapping / methods
Comparative Genomic Hybridization
Crosses, Genetic
Estradiol / metabolism
Estrogens / metabolism*
Female
Gene Dosage
Gene Expression Regulation, Neoplastic*
Genetic Predisposition to Disease*
Genetic Variation
Genotype
Mammary Neoplasms, Animal / genetics*
Phenotype
Quantitative Trait Loci
Rats
Time Factors
Grant Support
ID/Acronym/Agency:
P20-RR16469/RR/NCRR NIH HHS; P30 CA014520/CA/NCI NIH HHS; P30-CA014520/CA/NCI NIH HHS; P30-CA036727/CA/NCI NIH HHS; R01 CA077876/CA/NCI NIH HHS; R01-CA77876/CA/NCI NIH HHS; T32-CA009135/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Estrogens; 4TI98Z838E/Estradiol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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