Authors:
MNC Fletcher, MAA Castro, X Wang, I de Santiago, M O'Reilly, S-F Chin, OM Rueda, C Caldas, BAJ Ponder, F Markowetz, KB Meyer
Journal name: 
Nat Commun
Citation info: 
4:2464
Abstract: 
The fibroblast growth factor receptor 2 (FGFR2) locus has been consistently identified as a breast cancer risk locus in independent genome-wide association studies. However, the molecular mechanisms underlying FGFR2-mediated risk are still unknown. Using model systems we show that FGFR2-regulated genes are preferentially linked to breast cancer risk loci in expression quantitative trait loci analysis, supporting the concept that risk genes cluster in pathways. Using a network derived from 2,000 transcriptional profiles we identify SPDEF, ERα, FOXA1, GATA3 and PTTG1 as master regulators of fibroblast growth factor receptor 2 signalling, and show that ERα occupancy responds to fibroblast growth factor receptor 2 signalling. Our results indicate that ERα, FOXA1 and GATA3 contribute to the regulation of breast cancer susceptibility genes, which is consistent with the effects of anti-oestrogen treatment in breast cancer prevention, and suggest that fibroblast growth factor receptor 2 signalling has an important role in mediating breast cancer risk.
DOI: 
http://doi.org/10.1038/ncomms3464
Research group: 
Ponder Group, Caldas Group, Markowetz Group
E-pub date: 
31 Aug 2013