An "omics" approach to determine the mechanisms of acquired aromatase inhibitor resistance

OMICS. 2011 Jun;15(6):347-52. doi: 10.1089/omi.2010.0097. Epub 2011 Feb 19.

Abstract

Aromatase inhibitors (AIs) are the major types of drugs to treat hormone-dependent breast cancer. Although these drugs work effectively, cancer still recurs in many patients after treatment as a result of acquired resistance to the AIs. To characterize the resistant mechanisms, a set of MCF-7aro cell lines that acquired resistance to the AIs was generated. Through an "Omics" approach, we found that the resistance mechanisms of the three AIs (anastrozole, letrozole, and exemestane) differ and activation of estrogen receptor alpha (ERα) is critical for acquired AI resistance. Our results reveal that growth factor/signal transduction pathways are upregulated after ERα-dependent pathways are suppressed by AIs, and ERα can then be activated through different crosstalk mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology*
  • Aromatase Inhibitors / pharmacology*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Drug Resistance, Neoplasm / genetics*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression Profiling*
  • Genome-Wide Association Study
  • Humans
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / genetics*
  • Neoplasms, Hormone-Dependent / metabolism

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Estrogen Receptor alpha