Master regulators of FGFR2 signalling and breast cancer risk

نویسندگان

  • Michael N. C. Fletcher
  • Mauro A. A. Castro
  • Xin Wang
  • Ines de Santiago
  • Martin O’Reilly
  • Suet-Feung Chin
  • Oscar M. Rueda
  • Carlos Caldas
  • Bruce A. J. Ponder
  • Florian Markowetz
  • Kerstin B. Meyer
چکیده

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.

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Vignette for Fletcher2013b: master regulators of FGFR2 signalling and breast cancer risk

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عنوان ژورنال:

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2013