Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24601-0477, USA.
Breast Cancer Res Treat. 2011 Nov;130(1):41-8. doi: 10.1007/s10549-010-1237-9. Epub 2010 Dec 10.
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.
我们对大约 500 名患者和志愿者的雌激素相关受体γ基因（ERR-γ）5'UTR 进行了测序，发现与健康志愿者相比，乳腺癌患者的生殖系中（AAAG）（n）微卫星的较长等位基因更有可能存在。该微卫星区域包含多个转录因子的多个结合位点，我们假设 ERR-γ 5'UTR 区域中含有的多态性 AAAG 序列可能调节 ERR-γ 的表达。我们发现含有 AAAG 重复序列的 369bp PCR 产物可驱动雌激素受体阳性乳腺癌细胞中报告基因的表达。我们的结果支持 5'UTR 区域在 ERR-γ 表达中的作用，这可能是通过与可变串联 AAAG 重复结合介导的，其长度与乳腺癌易感性相关。我们的研究表明，ERR-γ 基因 5'UTR 区域的 AAAG 四核苷酸重复多态性可能是乳腺癌遗传易感性的一个新的生物标志物。
