RGD Reference Report - Mapping of three genetic determinants of susceptibility to estrogen-induced mammary cancer within the Emca8 locus on rat chromosome 5.

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Mapping of three genetic determinants of susceptibility to estrogen-induced mammary cancer within the Emca8 locus on rat chromosome 5.
Authors:	Schaffer, BS Leland-Wavrin, KM Kurz, SG Colletti, JA Seiler, NL Warren, CL Shull, JD
Citation:	Schaffer BS, etal., Cancer Prev Res (Phila). 2013 Jan;6(1):59-69. doi: 10.1158/1940-6207.CAPR-12-0346-T. Epub 2012 Nov 14.
RGD ID:	7364727
Pubmed:	(View Article at PubMed) PMID:23151807
DOI:	Full-text: DOI:10.1158/1940-6207.CAPR-12-0346-T
The ACI rat model of 17beta-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. (c)2012 AACR.

Annotation Click to see Annotation Detail View

Disease Annotations

Breast Neoplasms (IAGP)

Mammary Neoplasms, Experimental (IAGP)

Phenotype Annotations

Mammalian Phenotype

increased mammary adenocarcinoma incidence (IDA)

increased tumor latency (IAGP)

Objects Annotated

QTLs

Emca11 (Estrogen-induced mammary cancer QTL 11)

Emca12 (Estrogen-induced mammary cancer QTL 12)

Emca13 (Estrogen-induced mammary cancer QTL 13)

Strains

ACI.BN-(D5Mgh17-D5Mgh15)/Shul (NA)

ACI.BN-(D5Mgh17-D5Rat98)/Shul (NA)

ACI.BN-(D5Rat113-D5Rat159)/Shul (NA)

ACI.BN-(D5Rat113-D5Rat36)/Shul (NA)

ACI.BN-(D5Rat60-D5Rat115)/Shul (NA)

ACI.BN-(D5Rat72-D5Rat36)/Shul (NA)

ACI.BN-(D5Uwm70-D5Mgh15)/Shul (NA)

ACI.BN-(D5Uwm70-D5Rat32)/Shul (NA)

ACI/SegHsd (NA)

Objects referenced in this article

Strain	ACI.BN-(D5Uwm70-D5Got42)/Shul	null	Rattus norvegicus
QTL	Emca8	Estrogen-induced mammary cancer QTL 8	Rattus norvegicus

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Mapping of three genetic determinants of susceptibility to estrogen-induced mammary cancer within the Emca8 locus on rat chromosome 5.

Mammalian Phenotype