Autoantibodies Specific to ERalpha are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer

A. Maselli, S. Parlato, R. Puglisi, C. Raggi, M. Spada, D. Macchia, G. Pontecorvi, E. Iessi, M. T. Pagano, F. Cirulli, L. Gabriele, A. Care, P. Vici, L. Pizzuti, M. Barba, P. Matarrese, M. Pierdominici, E. Ortona

Research output: Contribution to journalArticle

Abstract

Tamoxifen resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. The mechanisms of tamoxifen resistance are not fully understood although several underlying molecular events have been suggested. Recently, we identified autoantibodies reacting with membrane-associated ERalpha (anti-ERalpha Abs) in sera of breast cancer patients, able to promote tumor growth. Here, we investigated whether anti-ERalpha Abs purified from sera of ER-positive breast cancer patients could contribute to tamoxifen resistance. Anti-ERalpha Abs inhibited tamoxifen-mediated effects on cell cycle and proliferation in MCF-7 cells. Moreover, anti-ERalpha Abs hampered the tamoxifen-mediated reduction of tumor growth in SCID mice xenografted with breast tumor. Notably, simvastatin-mediated disaggregation of lipid rafts, where membrane-associated ERalpha is embedded, restored tamoxifen sensitivity, preventing anti-ERalpha Abs effects. In conclusion, detection of serum anti-ERalpha Abs may help predict tamoxifen resistance and concur to appropriately inform therapeutic decisions concerning hormone therapy in ER-positive breast cancer patients.
Original languageItalian
Pages (from-to)E750
JournalCells
Volume8
Issue number7
DOIs
Publication statusPublished - 2019

Cite this

Maselli, A., Parlato, S., Puglisi, R., Raggi, C., Spada, M., Macchia, D., Pontecorvi, G., Iessi, E., Pagano, M. T., Cirulli, F., Gabriele, L., Care, A., Vici, P., Pizzuti, L., Barba, M., Matarrese, P., Pierdominici, M., & Ortona, E. (2019). Autoantibodies Specific to ERalpha are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer. Cells, 8(7), E750. https://doi.org/10.3390/cells8070750