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Master regulators of FGFR2 signalling and breast cancer risk

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 ge...

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Detalles Bibliográficos
Autores principales: Fletcher, Michael N. C., Castro, Mauro A. A., Wang, Xin, de Santiago, Ines, O’Reilly, Martin, Chin, Suet-Feung, Rueda, Oscar M., Caldas, Carlos, Ponder, Bruce A. J., Markowetz, Florian, Meyer, Kerstin B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778544/
https://www.ncbi.nlm.nih.gov/pubmed/24043118
http://dx.doi.org/10.1038/ncomms3464
Descripción
Sumario: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.