PMID- 22993404
OWN - NLM
STAT- MEDLINE
DCOM- 20130305
LR  - 20211021
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 72
IP  - 22
DP  - 2012 Nov 15
TI  - Rat Mcs1b is concordant to the genome-wide association-identified breast cancer 
      risk locus at human 5q11.2 and MIER3 is a candidate cancer susceptibility gene.
PG  - 6002-12
LID - 10.1158/0008-5472.CAN-12-0748 [doi]
AB  - Low-penetrance alleles associated with breast cancer risk have been identified in 
      population-based studies. Most risk loci contain either no or multiple potential 
      candidate genes. Rat mammary carcinoma susceptibility 1b (Mcs1b) is a 
      quantitative trait locus on RN02 that confers decreased susceptibility when 
      Copenhagen (COP)-resistant alleles are introgressed into a Wistar Furth 
      (WF)-susceptible genome. Five WF.COP congenic lines containing COP RN02 segments 
      were compared. One line developed an average of 3.4 +/- 2.0 and 5.5 +/- 3.6 mammary 
      carcinomas per rat +/- SD when females were Mcs1b-resistant homozygous and Mcs1b 
      heterozygous, respectively. These phenotypes were significantly different from 
      susceptible genotype littermates (7.8 +/- 3.1 mean mammary carcinomas per rat +/- SD, 
      P = 0.0001 and P = 0.0413, respectively). All other congenic lines tested were 
      susceptible. Thus, Mcs1b was narrowed to 1.8 Mb of RN02 between genetic markers 
      ENSRNOSNP2740854 and g2UL2-27. Mammary gland-graft carcinoma susceptibility 
      assays were used to determine that donor (P = 0.0019), but not recipient Mcs1b 
      genotype (P = 0.9381), was associated with ectopic mammary carcinoma outcome. Rat 
      Mcs1b contains sequence orthologous to human 5q11.2, a breast cancer 
      susceptibility locus identified in multiple genome-wide association studies. 
      Human/rat MAP3K1/Map3k1 and mesoderm induction early response (MIER; MIER3)/MIER3 
      are within these orthologous segments. We identified MIER3 as a candidate Mcs1b 
      gene based on 4.5-fold higher mammary gland levels of MIER3 transcripts in 
      susceptible compared with Mcs1b-resistant females. These data suggest that the 
      human 5q11.2 breast cancer risk allele marked by rs889312 is mammary gland 
      autonomous, and MIER3 is a candidate breast cancer susceptibility gene.
CI  - (c)2012 AACR.
FAU - denDekker, Aaron D
AU  - denDekker AD
AD  - Center for Genetics and Molecular Medicine, Department of Biochemistry and 
      Molecular Biology, and James Graham Brown Cancer Center, University of 
      Louisville, Louisville, Kentucky 40292, USA.
FAU - Xu, Xin
AU  - Xu X
FAU - Vaughn, M Derek
AU  - Vaughn MD
FAU - Puckett, Aaron H
AU  - Puckett AH
FAU - Gardner, Louis L
AU  - Gardner LL
FAU - Lambring, Courtney J
AU  - Lambring CJ
FAU - Deschenes, Lucas
AU  - Deschenes L
FAU - Samuelson, David J
AU  - Samuelson DJ
LA  - eng
GR  - R01 CA137052/CA/NCI NIH HHS/United States
GR  - P30 ES014443/ES/NIEHS NIH HHS/United States
GR  - P30ES014443/ES/NIEHS NIH HHS/United States
GR  - R01CA137052/CA/NCI NIH HHS/United States
GR  - T32 ES011564/ES/NIEHS NIH HHS/United States
GR  - T35 ES014559/ES/NIEHS NIH HHS/United States
GR  - ES014443/ES/NIEHS NIH HHS/United States
GR  - CA137052/CA/NCI NIH HHS/United States
GR  - T35ES014559-06/ES/NIEHS NIH HHS/United States
GR  - T32ES011564/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120919
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (MIER3 protein, human)
RN  - 0 (Nuclear Proteins)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Animals, Congenic
MH  - Body Weight/genetics
MH  - Breast Neoplasms/*genetics
MH  - Cell Nucleus/genetics/metabolism
MH  - Chromosome Mapping
MH  - *Chromosomes, Human, Pair 5
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Humans
MH  - Mammary Neoplasms, Experimental/*genetics
MH  - Nuclear Proteins/*genetics/metabolism
MH  - Open Reading Frames
MH  - Rats
MH  - Transcription, Genetic
PMC - PMC3500408
MID - NIHMS409174
COIS- Potential conflicts of interest: None.
EDAT- 2012/09/21 06:00
MHDA- 2013/03/06 06:00
PMCR- 2013/11/15
CRDT- 2012/09/21 06:00
PHST- 2012/09/21 06:00 [entrez]
PHST- 2012/09/21 06:00 [pubmed]
PHST- 2013/03/06 06:00 [medline]
PHST- 2013/11/15 00:00 [pmc-release]
AID - 0008-5472.CAN-12-0748 [pii]
AID - 10.1158/0008-5472.CAN-12-0748 [doi]
PST - ppublish
SO  - Cancer Res. 2012 Nov 15;72(22):6002-12. doi: 10.1158/0008-5472.CAN-12-0748. Epub 
      2012 Sep 19.