Journal article
FOXA1 is an essential determinant of ERα expression and mammary ductal morphogenesis
GM Bernardo, KL Lozada, JD Miedler, G Harburg, SC Hewitt, JD Mosley, AK Godwin, KS Korach, JE Visvader, KH Kaestner, FW Abdul-Karim, MM Montano, RA Keri
Development | COMPANY BIOLOGISTS LTD | Published : 2010
DOI: 10.1242/dev.043299
Abstract
FOXA1, estrogen receptor α (ERα) and GATA3 independently predict favorable outcome in breast cancer patients, and their expression correlates with a differentiated, luminal tumor subtype. As transcription factors, each functions in the morphogenesis of various organs, with ERα and GATA3 being established regulators of mammary gland development. Interdependency between these three factors in breast cancer and normal mammary development has been suggested, but the specific role for FOXA1 is not known. Herein, we report that Foxa1 deficiency causes a defect in hormone-induced mammary ductal invasion associated with a loss of terminal end bud formation and ERa expression. By contrast, Foxa1 null..
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Awarded by National Institute of Diabetes and Digestive and Kidney Diseases
Funding Acknowledgements
We thank Kay-Uwe Wagner and Jennifer Yori for instruction in performing orthotopic transplants, Marie-Liesse Asselin-Labat for assistance with Gata3 deficient mice and Yanduan Hu for technical support for the ChIP analyses. Paraffin embedding and sectioning was performed by the Case Western Reserve University Tissue Procurement and Histology Core Facility. The CK8 antibody was developed by Philippe Brulet and Rolf Kemler, and obtained from the Developmental Studies Hybridoma Bank formed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242, USA. G. M. B. is supported through a predoctoral fellowship from the Department of Defense (DoD) (W81XWH-06-1-0712). This work was also supported by the Case Western Reserve University Comprehensive Cancer Center (P30 CA043703), a University Hospitals of Cleveland Pathology Research Associates Grant (F. W. A. K. and R. A. K.), the Division of Intramural Research of the National Institute of Environmental Health Sciences/NIH (S. C. H. and K. S. K.), an Ohio Innovation Incentive Fellowship (J. D. Mosley.), the NIH (T32-GM0720, J. D. Mosley; P01 DK049210, K. H. K.; R01 CA090398, R. A. K.), a Fox Chase Cancer Center Support Grant (P30 CA006927, A. K. G.), the National Health and Medical Research Council of Australia (J. E. V.) and the DoD (W81XWH-08-1-0347, R. A. K.). Deposited in PMC for release after 12 months.