Identification of MAGEA antigens as causal players in the development of tamoxifen-resistant breast cancer
Abstract
The antiestrogen tamoxifen is a well-tolerated, effective treatment for estrogen receptor-α-positive (ER+) breast cancer, but development of resistance eventually limits its use. Here we show that expression of MAGEA2, and related members of this cancer-testis antigen family, is upregulated in tamoxifen-resistant tumor cells. Expression of MAGEA2 in tumor lines grown in vitro or as xenografts led to continued proliferation in the presence of tamoxifen. At the molecular level, we demonstrate that MAGEA2 protein localizes to the nucleus and forms complexes with p53 and ERα, resulting in repression of the p53 pathway but increased ER-dependent signaling. In a series of ER+, tamoxifen-treated breast cancer patients, we show a highly significant (P=0.006) association between MAGEA (melanoma-associated antigen) expression and reduced overall survival, confirming the clinical significance of our observations.
Read the paper
Related studies
- A Coupled SYSTEM of Intracellular Ca 2+ Clocks and Surface Membrane Voltage Clocks Controls the Timekeeping Mechanism of the Heart’s Pacemaker
- A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin
- Cancer epigenetics: Moving forward
- Current developments in LC-MS for pharmaceutical analysis
- Myricetin: A comprehensive review on its biological potentials
- A Computational Systems Biology Software Platform for Multiscale Modeling and Simulation: Integrating Whole-Body Physiology, Disease Biology, and Molecular Reaction Networks
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.