Journal article
The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway
Proceedings of the National Academy of Sciences - PNAS, Vol.109(8), pp.2736-2741
02/21/2012
DOI: 10.1073/pnas.1018859108
PMCID: PMC3286915
PMID: 21690342
Abstract
Multiple factors including long-term treatment with tamoxifen are involved in the development of selective estrogen receptor (ER) modulator resistance in ER alpha-positive breast cancer. Many underlying molecular events that confer resistance are known but a unifying theme is yet to be revealed. In this report, we provide evidence that HOXB7 overexpression renders MCF-7 cells resistant to tamoxifen via cross-talk between receptor tyrosine kinases and ER alpha signaling. HOXB7 is an ER alpha-responsive gene. Extended treatment of MCF-7 cells with tamoxifen resulted in progressively increasing levels of HOXB7 expression, along with EGFR and EGFR ligands. Up-regulation of EGFR occurs through direct binding of HOXB7 to the EGFR promoter, enhancing transcriptional activity. Finally, higher expression levels of HOXB7 in the tumor significantly correlated with poorer disease-free survival in ER alpha-positive patients with breast cancer on adjuvant tamoxifen monotherapy. These studies suggest that HOXB7 acts as a key regulator, orchestrating a major group of target molecules in the oncogenic hierarchy. Functional antagonism of HOXB7 could circumvent tamoxifen resistance.
Details
- Title: Subtitle
- The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway
- Creators
- Kideok Jin - Johns Hopkins MedicineXiangjun Kong - Univ. of Sci. and Tech. of ChinaTariq Shah - Johns Hopkins UniversityMarie-France Penet - Johns Hopkins UniversityFlonne Wildes - Johns Hopkins UniversityDennis C. Sgroi - Harvard UniversityXiao-Jun Ma - AviaraDxYi Huang - University of PittsburghAnne Kallioniemi - Tampere UniversityGoran Landberg - University of ManchesterIvan Bieche - Institut CurieXinyan Wu - Johns Hopkins UniversityPeter E. Lobie - National University of SingaporeNancy E. Davidson - University of PittsburghZaver M. Bhujwalla - Johns Hopkins UniversityTao Zhu - Univ. of Sci. and Tech. of ChinaSaraswati Sukumar - Johns Hopkins University
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.109(8), pp.2736-2741
- DOI
- 10.1073/pnas.1018859108
- PMID
- 21690342
- PMCID
- PMC3286915
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- Natl Acad Sciences
- Number of pages
- 6
- Grant note
- P50-CA88843 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 2010CB912804; 2007CB914801; 2011CBA01103 / National Key Scientific Program of China P50CA088843 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 30971492; 30725015 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC) Susan G. Komen Postdoctoral Fellowships
- Language
- English
- Date published
- 02/21/2012
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984383918102771
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