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

Research output: Contribution to journalArticlepeer-review

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 ERα (anti-ERα Abs) in sera of breast cancer patients, able to promote tumor growth. Here, we investigated whether anti-ERα Abs purified from sera of ER-positive breast cancer patients could contribute to tamoxifen resistance. Anti-ERα Abs inhibited tamoxifen-mediated effects on cell cycle and proliferation in MCF-7 cells. Moreover, anti-ERα 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 ERα is embedded, restored tamoxifen sensitivity, preventing anti-ERα Abs effects. In conclusion, detection of serum anti-ERα Abs may help predict tamoxifen resistance and concur to appropriately inform therapeutic decisions concerning hormone therapy in ER-positive breast cancer patients.

Original languageEnglish
JournalCells
Volume8
Issue number7
DOIs
Publication statusPublished - Jul 19 2019

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antineoplastic Agents, Hormonal/immunology
  • Autoantibodies/blood
  • Breast Neoplasms/drug therapy
  • Drug Resistance, Neoplasm/immunology
  • Estrogen Receptor alpha/immunology
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, SCID
  • Middle Aged
  • Tamoxifen/therapeutic use
  • Xenograft Model Antitumor Assays

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