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The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 2/21/2012, Vol. 109 Issue 8, p2736-2741. 6p. - Publication Year :
- 2012
-
Abstract
- Multiple factors including long-term treatment with tamoxifen are involved in the development of selective estrogen receptor (ER) modulator resistance in ERα-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 ERα signaling. HOXB7 is an ERα-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 ERα-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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 109
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 72154681
- Full Text :
- https://doi.org/10.1073/pnas.1018859108