Master regulators of FGFR2 signalling and breast cancer risk

被引：164

作者：

Fletcher, Michael N. C. ^{[1
,2
]}

Castro, Mauro A. A. ^{[1
]}

Wang, Xin ^{[1
,2
]}

de Santiago, Ines ^{[1
]}

O'Reilly, Martin ^{[1
]}

Chin, Suet-Feung ^{[1
,2
]}

Rueda, Oscar M. ^{[1
,2
]}

Caldas, Carlos ^{[1
,2
]}

Ponder, Bruce A. J. ^{[1
,2
]}

Markowetz, Florian ^{[1
]}

Meyer, Kerstin B. ^{[1
,2
]}

机构：

[1] Univ Cambridge, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England

[2] Univ Cambridge, Dept Oncol, Li Ka Shing Ctr, Cambridge CB2 0RE, England

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

GENOME-WIDE ASSOCIATION; ETS TRANSCRIPTION FACTOR; ESTROGEN-RECEPTOR-ALPHA; GENE-EXPRESSION; TUMOR-METASTASIS; ER-ALPHA; NETWORKS; FOXA1; REVEALS; BINDING;

D O I：

10.1038/ncomms3464

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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, ER alpha, FOXA1, GATA3 and PTTG1 as master regulators of fibroblast growth factor receptor 2 signalling, and show that ER alpha occupancy responds to fibroblast growth factor receptor 2 signalling. Our results indicate that ER alpha, 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.

引用

页数：12

共 57 条

[1] The origins of estrogen receptor alpha-positive and estrogen receptor alpha-negative human breast cancer [J].

Allred, DC ;

Brown, P ;

Medina, D .

BREAST CANCER RESEARCH, 2004, 6 (06) :240-245

[2]

[Anonymous], 2011, R LANG ENV STAT COMP

[3] MEME SUITE: tools for motif discovery and searching [J].

Bailey, Timothy L. ;

Boden, Mikael ;

Buske, Fabian A. ;

Frith, Martin ;

Grant, Charles E. ;

Clementi, Luca ;

Ren, Jingyuan ;

Li, Wilfred W. ;

Noble, William S. .

NUCLEIC ACIDS RESEARCH, 2009, 37 :W202-W208

[4] Reverse engineering of regulatory networks in human B cells [J].

Basso, K ;

Margolin, AA ;

Stolovitzky, G ;

Klein, U ;

Dalla-Favera, R ;

Califano, A .

NATURE GENETICS, 2005, 37 (04) :382-390

[5] Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis [J].

Bernal, JA ;

Luna, R ;

Espina, A ;

Lázaro, I ;

Ramos-Morales, F ;

Romero, F ;

Arias, C ;

Silva, A ;

Tortolero, M ;

Pintor-Toro, JA .

NATURE GENETICS, 2002, 32 (02) :306-311

[6] FOXA1 is an essential determinant of ERα expression and mammary ductal morphogenesis [J].

Bernardo, Gina M. ;

Lozada, Kristen L. ;

Miedler, John D. ;

Harburg, Gwyndolen ;

Hewitt, Sylvia C. ;

Mosley, Jonathan D. ;

Godwin, Andrew K. ;

Korach, Kenneth S. ;

Visvader, Jane E. ;

Kaestner, Klaus H. ;

Abdul-Karim, Fadi W. ;

Montano, Monica M. ;

Keri, Ruth A. .

DEVELOPMENT, 2010, 137 (12) :2045-2054

[7] The transcriptional network for mesenchymal transformation of brain tumours [J].

Carro, Maria Stella ;

Lim, Wei Keat ;

Alvarez, Mariano Javier ;

Bollo, Robert J. ;

Zhao, Xudong ;

Snyder, Evan Y. ;

Sulman, Erik P. ;

Anne, Sandrine L. ;

Doetsch, Fiona ;

Colman, Howard ;

Lasorella, Anna ;

Aldape, Ken ;

Califano, Andrea ;

Iavarone, Antonio .

NATURE, 2010, 463 (7279) :318-U68

[8] Genome-wide analysis of estrogen receptor binding sites [J].

Carroll, Jason S. ;

Meyer, Clifford A. ;

Song, Jun ;

Li, Wei ;

Geistlinger, Timothy R. ;

Eeckhoute, Jerome ;

Brodsky, Alexander S. ;

Keeton, Erika Krasnickas ;

Fertuck, Kirsten C. ;

Hall, Giles F. ;

Wang, Qianben ;

Bekiranov, Stefan ;

Sementchenko, Victor ;

Fox, Edward A. ;

Silver, Pamela A. ;

Gingeras, Thomas R. ;

Liu, X. Shirley ;

Brown, Myles .

NATURE GENETICS, 2006, 38 (11) :1289-1297

[9] RedeR: R/Bioconductor package for representing modular structures, nested networks and multiple levels of hierarchical associations [J].

Castro, Mauro A. A. ;

Wang, Xin ;

Fletcher, Michael N. C. ;

Meyer, Kerstin B. ;

Markowetz, Florian .

GENOME BIOLOGY, 2012, 13 (04)

[10] Breast cancer risk-associated SNPs modulate the affinity of chromatin for FOXA1 and alter gene expression [J].

Cowper-Sal-lari, Richard ;

Zhang, Xiaoyang ;

Wright, Jason B. ;

Bailey, Swneke D. ;

Cole, Michael D. ;

Eeckhoute, Jerome ;

Moore, Jason H. ;

Lupien, Mathieu .

NATURE GENETICS, 2012, 44 (11) :1191-1198

← 1 2 3 4 5 6 →