TY - JOUR
T1 - Master regulators of FGFR2 signalling and breast cancer risk
AU - Fletcher, Michael N. C.
AU - Castro, Mauro A. A.
AU - Wang, Xin
AU - De Santiago, Ines
AU - O'Reilly, Martin
AU - Chin, Suet-Feung
AU - Rueda, Oscar M.
AU - Caldas, Carlos
AU - Ponder, Bruce A. J.
AU - Markowetz, Florian
AU - Meyer, Kerstin B.
PY - 2013
Y1 - 2013
N2 - 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. © 2013 Macmillan Publishers Limited. All rights reserved.
AB - 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. © 2013 Macmillan Publishers Limited. All rights reserved.
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U2 - 10.1038/ncomms3464
DO - 10.1038/ncomms3464
M3 - RGC 21 - Publication in refereed journal
C2 - 24043118
SN - 2041-1723
VL - 4
JO - Nature Communications
JF - Nature Communications
M1 - 2464
ER -
