Identification of MAGEA antigens as causal players in the development of tamoxifen-resistant breast cancer
Copyright policy )Identification of MAGEA antigens as causal players in the development of tamoxifen-resistant breast cancer
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.
- University of Aberdeen United Kingdom
- Guy's and St Thomas' NHS Foundation Trust United Kingdom
- Kings College London, University of London United Kingdom
- Queen Mary University of London United Kingdom
- Guy's Hospital United Kingdom
EXPRESSION, 570, Supplementary Data, TUMOR-CELLS, PROTEIN, 610, Breast Neoplasms, MECHANISMS, RC0254, Mice, Breast cancer, SDG 3 - Good Health and Well-being, Cell Line, Tumor, Animals, Humans, RECURRENCE, Cell Proliferation, Cell Nucleus, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Gene Expression Profiling, CANCER/TESTIS ANTIGENS, REPRESSION, Estrogen Antagonists, Estrogen Receptor alpha, Hep G2 Cells, MODIFIED RADICAL-MASTECTOMY, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Cancer therapeutic resistance, Tamoxifen, P53-DEPENDENT APOPTOSIS, Drug Resistance, Neoplasm, Cancer Research UK, Tumor immunology, MCF-7 Cells, COMPLEXES, Original Article, Female, Tumor Suppressor Protein p53, Melanoma-Specific Antigens, Neoplasm Transplantation
EXPRESSION, 570, Supplementary Data, TUMOR-CELLS, PROTEIN, 610, Breast Neoplasms, MECHANISMS, RC0254, Mice, Breast cancer, SDG 3 - Good Health and Well-being, Cell Line, Tumor, Animals, Humans, RECURRENCE, Cell Proliferation, Cell Nucleus, RC0254 Neoplasms. Tumors. Oncology (including Cancer), Gene Expression Profiling, CANCER/TESTIS ANTIGENS, REPRESSION, Estrogen Antagonists, Estrogen Receptor alpha, Hep G2 Cells, MODIFIED RADICAL-MASTECTOMY, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Cancer therapeutic resistance, Tamoxifen, P53-DEPENDENT APOPTOSIS, Drug Resistance, Neoplasm, Cancer Research UK, Tumor immunology, MCF-7 Cells, COMPLEXES, Original Article, Female, Tumor Suppressor Protein p53, Melanoma-Specific Antigens, Neoplasm Transplantation
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