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

作者：Galindo C L; McCormick J F; Bubb V J; Alkadem D H Abid; Li Long Shan; McIver L J; George A C; Boothman D A; Quinn J P; Skinner M A; Garner H R^*

来源：Breast Cancer Research and Treatment, 2011, 130(1): 41-48.

DOI：10.1007/s10549-010-1237-9

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

We sequenced the 5' UTR of the estrogen-related receptor gamma gene (ERR-gamma) in similar to 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-gamma might modulate expression of ERR-gamma. 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-gamma 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-gamma gene 5' UTR region may be a new biomarker for genetic susceptibility to breast cancer.

• 出版日期2011-11