Human Gene Set: WELCSH_BRCA1_TARGETS_UP


Standard name WELCSH_BRCA1_TARGETS_UP
Systematic name M5490
Brief description Up-regulated by induction of exogenous BRCA1 in EcR-293 cells
Full description or abstract Loss of function of BRCA1 caused by inherited mutation and tissue-specific somatic mutation leads to breast and ovarian cancer. Nearly all BRCA1 germ-line mutations involve truncation or loss of the C-terminal BRCT transcriptional activation domain, suggesting that transcriptional regulation is a critical function of the wild-type gene. The purpose of this project was to determine whether there is a link between the role of BRCA1 in transcriptional regulation and its role in tumor suppression. We developed a cell line (in which BRCA1 can be induced) and used microarray analysis to compare transcription profiles of epithelial cells with low endogenous levels of BRCA1 vs. transcription profiles of cells with 2-4-fold higher induced levels of expression of BRCA1. At these levels of expression, BRCA1 did not induce apoptosis. Undirected cluster analysis of six paired experiments revealed 373 genes, the expression of which was altered significantly and consistently by BRCA1 induction. Expression of 62 genes was altered more than 2-fold. BRCA1-regulated genes associated with breast tumorigenesis included the estrogen-responsive genes MYC and cyclin D1, which are overexpressed in many breast tumors; STAT1 and JAK1, key components of the cytokine signal transduction pathway; the extracellular matrix protein laminin 3A; ID4, an inhibitor of DNA-binding transcriptional activators, which in turn negatively regulates BRCA1 expression; and the prohormone stanniocalcin, expression of which is lost in breast tumor cells. Coordinated expression of BRCA1 with ID4 and with stanniocalcin was confirmed in primary breast and ovarian tumors.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 12032322   Authors: Welcsh PL,Lee MK,Gonzalez-Hernandez RM,Black DJ,Mahadevappa M,Swisher EM,Warrington JA,King MC
Exact source Table 4S: mean(BRCA1+)/mean(BRCA1-) > 1
Related gene sets (show 1 additional gene sets from the source publication)

(show 3 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by John Newman (University of Washington)
Source platform or
identifier namespace		 AFFY_HuGene
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 201 genes
Gene families ? Categorize these 201 genes by gene family
Show members (show 223 source identifiers mapped to 201 genes)
Version history 3.1: WELCSH_BRCA1_TARGETS_1_UP

See MSigDB license terms here. Please note that certain gene sets have special access terms.