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Nat Commun. 2013;4:2464. doi: 10.1038/ncomms3464.

Master regulators of FGFR2 signalling and breast cancer risk.

Author information

1
1] Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK [2] Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK [3] [4].

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.

PMID:
24043118
PMCID:
PMC3778544
DOI:
10.1038/ncomms3464
[Indexed for MEDLINE]
Free PMC Article
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