Preclinical study

Breast Cancer Research and Treatment

, Volume 130, Issue 1, pp 41-48

A long AAAG repeat allele in the 5′ UTR of the ERR-γ gene is correlated with breast cancer predisposition and drives promoter activity in MCF-7 breast cancer cells

  • C. L. GalindoAffiliated withVirginia Bioinformatics Institute, Virginia Polytechnic Institute and State University
  • , J. F. McCormickAffiliated withVirginia Bioinformatics Institute, Virginia Polytechnic Institute and State University
  • , V. J. BubbAffiliated withSchool of Biomedical Sciences, University of Liverpool
  • , D. H. Abid AlkademAffiliated withSchool of Biomedical Sciences, University of Liverpool
  • , Long-Shan LiAffiliated withSimmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center
  • , L. J. McIverAffiliated withVirginia Bioinformatics Institute, Virginia Polytechnic Institute and State University
  • , A. C. GeorgeAffiliated withVirginia Bioinformatics Institute, Virginia Polytechnic Institute and State University
  • , D. A. BoothmanAffiliated withSimmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center
  • , J. P. QuinnAffiliated withSchool of Biomedical Sciences, University of Liverpool
    • , M. A. SkinnerAffiliated withDepartment of Surgery, University of Texas Southwestern Medical CenterChildren’s Medical Center
    • , H. R. GarnerAffiliated withVirginia Bioinformatics Institute, Virginia Polytechnic Institute and State University Email author 

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

Abstract

We sequenced the 5′ UTR of the estrogen-related receptor gamma gene (ERR-γ) in ~500 patient and volunteer samples and found that longer alleles of the (AAAG) n microsatellite were statistically and significantly more likely to exist in the germlines of breast cancer patients when compared to healthy volunteers. This microsatellite region contains multiple binding sites for a number of transcription factors, and we hypothesized that the polymorphic AAAG-containing sequence in the 5′ UTR region of ERR-γ might modulate expression of ERR-γ. We found that the 369 bp PCR product containing the AAAG repeat drove expression of a reporter gene in estrogen receptor positive breast cancer cells. Our results support a role for the 5′ UTR region in ERR-γ expression, which is potentially mediated via binding to the variable tandem AAAG repeat, the length of which correlates with breast cancer pre-disposition. Our study indicates that the AAAG tetranucleotide repeat polymorphism in ERR-γ gene 5′ UTR region may be a new biomarker for genetic susceptibility to breast cancer.

Keywords

Microsatellite Breast cancer AAAG Polymorphism Genetic predisposition