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. Galindo
  • J. F. McCormick
  • V. J. Bubb
  • D. H. Abid Alkadem
  • Long-Shan Li
  • L. J. McIver
  • A. C. George
  • D. A. Boothman
  • J. P. Quinn
  • M. A. Skinner
  • H. R. Garner
Preclinical study


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.


Microsatellite Breast cancer AAAG Polymorphism Genetic predisposition 

Supplementary material

10549_2010_1237_MOESM1_ESM.doc (714 kb)
Supplementary material 1 (DOCX 714 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • C. L. Galindo
    • 1
  • J. F. McCormick
    • 1
  • V. J. Bubb
    • 3
  • D. H. Abid Alkadem
    • 3
  • Long-Shan Li
    • 2
  • L. J. McIver
    • 1
  • A. C. George
    • 1
  • D. A. Boothman
    • 2
  • J. P. Quinn
    • 3
  • M. A. Skinner
    • 4
    • 5
  • H. R. Garner
    • 1
  1. 1.Virginia Bioinformatics InstituteVirginia Polytechnic Institute and State UniversityBlacksburgUSA
  2. 2.Simmons Comprehensive Cancer CenterUniversity of Texas Southwestern Medical CenterDallasUSA
  3. 3.School of Biomedical SciencesUniversity of LiverpoolLiverpoolUK
  4. 4.Department of SurgeryUniversity of Texas Southwestern Medical CenterDallasUSA
  5. 5.Children’s Medical CenterDallasUSA

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