BRCA1-mediated repression of select X chromosome genes

被引：20

作者：

Jazaeri A.A. ^{[1
]}

Chandramouli G.V.R. ^{[1
]}

Aprelikova O. ^{[1
]}

Nuber U.A. ^{[2
]}

Sotiriou C. ^{[1
,3
]}

Liu E.T. ^{[1
,4
]}

Ropers H.H. ^{[2
]}

Yee C.J. ^{[5
]}

Boyd J. ^{[5
]}

Barrett J.C. ^{[1
]}

机构：

[1] Center for Cancer Research, National Cancer Institute, Bethesda, MD-20892-2440

[2] Max Planck Inst. for Molec. Genetics, 14195 Berlin

[3] Jules Bordet Institute, Microarray Unit, 1000 Brussels

[4] Genome Institute of Singapore, 117528 Singapore

[5] Department of Surgery, Memorial Sloan-Kettering Cancer Ctr., New York, NY 10021

来源：

Journal of Translational Medicine | / 2卷 / 1期

关键词：

HCC1937 Cell; BRCA1 Mutation Carrier; Sporadic Tumor; BRCA1 Expression; Unigene Cluster;

D O I：

10.1186/1479-5876-2-32

中图分类号：

学科分类号：

摘要：

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. Reexpression 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. © 2004 Jazaeri et al; licensee BioMed Central Ltd.

引用

页数：8

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