Uncovering BRCA1-regulated signalling pathways by microarray-based expression profiling

The introduction of microarray technology to the scientific and medical com munities has dramatically changed the way in which we now address basic bio medical questions. Expression profiling using microarrays facilitates an ex perimental approach where alterations in the transcript level of entire tra nscriptomes can be simultaneously assayed in response to defined stimuli. W e have used microarray analysis to identify downstream transcriptional targ ets of the BRCA1 (Breast Cancer 1) tumour-suppressor gene as a means of def ining its function. BRCA1 has been implicated in the predisposition to earl y onset breast and ovarian cancer and while its exact function remains to b e defined, roles in DNA repair, cell-cycle control and transcriptional regu lation have been implied. In the current study we have generated cell lines with tetracycline-regulated, inducible expression of BRCA1 as a tool to id entify genes, which might represent important effectors of BRCA1 function. Oligonucleotide array-based expression profiling identified a number of gen es that were upregulated at various times following inducible expression of BRCA1 including the DNA damage-responsive gene GADD45 (Growth Arrest after DNA Damage). Identified targets were confirmed by Northern blot analysis a nd their functional significance as BRCA1 targets examined.