BRCA1-mediated repression of select X chromosome genes
1 From the Center for Cancer Research of the National Cancer Institute. Building 31, Room 3A11, 31 Center Drive, MSC 2440, Bethesda, MD 20892-2440 USA
2 Max Planck Institute for Molecular Genetics. Ihnestrasse 73, 14195 Berlin Germany
3 Jules Bordet Institute. Microarray Unit, 121 Bld. de Waterloo, 1000 Brussels, Belgium
4 Genome Institute of Singapore, 1 Science Park Rd., The Capricorn #05-01, Singapore Sicence Park II 117528, Singapore
5 From the Departments of Surgery and Medicine of the Memorial Sloan-Kettering Cancer Center 1275 York Ave., New York, New York, 10021 USA
Journal of Translational Medicine 2004, 2:32 doi:10.1186/1479-5876-2-32Published: 21 September 2004
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.