title: BRCA1-mediated repression of select X chromosome genes.
abstract: Recently BRCA1 has been implicated in the regulation of gene expression from the X chromosome. In this study the influence of BRCA1 on expression of X chromosome genes was investigated. Complementary DNA microarrays were used to compare the expression levels of X chromosome genes in 18 BRCA1-associated ovarian cancers to those of the 13 "BRCA1-like" and 14 "BRCA2-like" sporadic tumors (as defined by previously reported expression profiling). Significance was determined using parametric statistics with P < 0.005 as a cutoff. Forty of 178 total X-chromosome transcripts were differentially expressed between the BRCA1-associated tumors and sporadic cancers with a BRCA2-like molecular profile. Thirty of these 40 genes showed higher mean expression in the BRCA1-associated samples including all 11 transcripts that mapped to Xp11. In contrast, four of 178 total X chromosome transcripts showed significant differential expression between BRCA1-associated and sporadic tumors with a BRCA1-like molecular profile. All four mapped to Xp11 and showed higher mean expression in BRCA1-associated tumors. Re-expression of BRCA1 in HCC1937 BRCA1-deficient breast cancer cell resulted in the repression of 21 transcripts. Eleven of the 21 (54.5%) transcripts mapped to Xp11. However, there was no significant overlap between these Xp11 genes and those found to be differentially expressed between BRCA1-associated and sporadic ovarian cancer samples. These results demonstrate that BRCA1 mediates the repression of several X chromosome genes, many of which map to the Xp11 locus.
authors.affiliation: Center for Cancer Research of the National Cancer Institute, Building 31, Room 3A11, 31 Center Drive, MSC 2440, Bethesda, MD 20892-2440 USA. barrett@mail.nih.gov
authors.forename: Amir A
authors.initials: AA
authors.lastname: Jazaeri
authors.forename: Gadisetti VR
authors.initials: GV
authors.lastname: Chandramouli
authors.forename: Olga
authors.initials: O
authors.lastname: Aprelikova
authors.forename: Ulrike A
authors.initials: UA
authors.lastname: Nuber
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Edison T
authors.initials: ET
authors.lastname: Liu
authors.forename: H Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Cindy J
authors.initials: CJ
authors.lastname: Yee
authors.forename: Jeff
authors.initials: J
authors.lastname: Boyd
authors.forename: J Carl
authors.initials: JC
authors.lastname: Barrett