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

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

We sequenced the 5′ UTR of the estrogenrelated 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.

Original languageEnglish (US)
Pages (from-to)41-48
Number of pages8
JournalBreast Cancer Research and Treatment
Volume130
Issue number1
DOIs
StatePublished - Nov 2011

Keywords

  • AAAG
  • Breast cancer
  • Genetic predisposition
  • Microsatellite
  • Polymorphism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Galindo, C. L., McCormick, J. F., Bubb, V. J., Abid Alkadem, D. H., Li, L. S., McIver, L. J., George, A. C., Boothman, D. A., Quinn, J. P., Skinner, M. A., & Garner, H. R. (2011). 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. Breast Cancer Research and Treatment, 130(1), 41-48. https://doi.org/10.1007/s10549-010-1237-9