Human Gene Set: BAE_BRCA1_TARGETS_UP


Standard name BAE_BRCA1_TARGETS_UP
Systematic name M2072
Brief description Genes concordantly up-regulated in DU-145 and MCF-7 cells (lprostate, breast cancer) upon expression of BRCA1.
Full description or abstract Mutations of the breast cancer susceptibility gene 1 (BRCA1), a tumor suppressor, confer an increased risk for breast, ovarian, and prostate cancers. To investigate the function of the BRCA1 gene, we performed DNA microarray and confirmatory reverse transcription-PCR analyses to identify BRCA1-regulated gene expression changes. We found that BRCA1 up-regulates the expression of multiple genes involved in the cytoprotective antioxidant response, including glutathione S-transferases, oxidoreductases, and other antioxidant genes. Consistent with these findings, BRCA1 overexpression conferred resistance while BRCA1 deficiency conferred sensitivity to several different oxidizing agents (hydrogen peroxide and paraquat). In addition, in the setting of oxidative stress (due to hydrogen peroxide), BRCA1 shifted the cellular redox balance to a higher ratio of reduced to oxidized glutathione. Finally, BRCA1 stimulated antioxidant response element-driven transcriptional activity and enhanced the activity of the antioxidant response transcription factor nuclear factor erythroid-derived 2 like 2 [also called NRF2 (NFE2L2)]. The ability of BRCA1 to stimulate antioxidant response element-dependent transcription and to protect cells against oxidative stress was attenuated by inhibition of nuclear factor erythroid-derived 2 like 2. These findings suggest a novel function for BRCA1, i.e., to protect cells against oxidative stress. This function would be consistent with the postulated role of BRCA1 as a caretaker gene in preserving genomic integrity.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15520196   Authors: Bae I,Fan S,Meng Q,Rih JK,Kim HJ,Kang HJ,Xu J,Goldberg ID,Jaiswal AK,Rosen EM
Exact source Table 5: Increased by BRCA1
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 HUMAN_SEQ_ACCESSION
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Version history 3.1: First introduced

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