Uncovering BRCAI-regulated signalling pathways by microarray-based expression profiling. (November 2001)

• Record Type: Journal Article
• Authors: Mullan, P. B.; McWilliams, S.; Quinn, J.; Andrews, H.; Gilmore, P.; McCabe, N.; McKenna, S.; Harkin, D. P.
• Is Part Of: Biochemical Society transactions. Volume 29:Number 6(2001)
• Page Start: 678
• Page End: 683
• Publication Date: 2001-11
• Subjects: expression profiling -- GADD45 -- oligonucleotide array; ATM, ataxia telangiectasia mutated -- MMS, methyl methanesulphonate; Biochemistry -- Congresses; 572
• DOI: 10.1042/bst0290678
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : The introduction of microarray technology to the scientific and medical communities has dramatically changed the way in which we now address basic biomedical questions. Expression profiling using microarrays facilitates an experimental approach where alterations in the transcript level of entire transcriptomes can be simultaneously assayed in response to defined stimuli. We have used microarray analysis to identify downstream transcriptional targets of the BRCA1 (Br east Ca ncer 1) tumour-suppressor gene as a means of defining its function. BRCA1 has been implicated in the predisposition to early onset breast and ovarian cancer and while its exact function remains to be defined, roles in DNA repair, cell-cycle control and transcriptional regulation have been implied. In the current study we have generated cell lines with tetracycline-regulated, inducible expression of BRCA1 as a tool to identify genes, which might represent important effectors of BRCA1 function. Oligonucleotide array-based expression profiling identified a number of genes that were upregulated at various times following inducible expression of BRCA1 including the DNA damage-responsive gene GADD45 (G rowth A rrest after D NA D amage). Identified targets were confirmed by Northern blot analysis and their functional significance as BRCA1 targets examined.