| First Author | Jin K | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 8 | Pages | 2736-41 |
| PubMed ID | 21690342 | Mgi Jnum | J:181819 |
| Mgi Id | MGI:5314211 | Doi | 10.1073/pnas.1018859108 |
| Citation | Jin K, et al. (2012) The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway. Proc Natl Acad Sci U S A 109(8):2736-41 |
| abstractText | Multiple factors including long-term treatment with tamoxifen are involved in the development of selective estrogen receptor (ER) modulator resistance in ERalpha-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 ERalpha signaling. HOXB7 is an ERalpha-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 ERalpha-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. |
