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.
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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., Galindo; J., McCormick; V., Bubb; D., Abid Alkadem; Long-Shan, Li; L., McIver; A., George; D., Boothman; J., Quinn; M., Skinner; H., Garner
Follow Breast Cancer Research and Treatment
, Volume 130 (1)
Springer Journals – Nov 1, 2011
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