title: 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.
abstract: 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.
authors.affiliation: Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24601-0477, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Galindo
authors.forename: J F
authors.initials: JF
authors.lastname: McCormick
authors.forename: V J
authors.initials: VJ
authors.lastname: Bubb
authors.forename: D H
authors.initials: DH
authors.lastname: Abid Alkadem
authors.forename: Long-Shan
authors.initials: LS
authors.lastname: Li
authors.forename: L J
authors.initials: LJ
authors.lastname: McIver
authors.forename: A C
authors.initials: AC
authors.lastname: George
authors.forename: D A
authors.initials: DA
authors.lastname: Boothman
authors.forename: J P
authors.initials: JP
authors.lastname: Quinn
authors.forename: M A
authors.initials: MA
authors.lastname: Skinner
authors.forename: H R
authors.initials: HR
authors.lastname: Garner
mesh_terms: D020121:5' Untranslated Regions; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; C425824:estrogen receptor gamma