Endocrine resistance in breast cancer : the role of estrogen receptor stability

Sarah A. Jeffreys, Branka Powter, Bavanthi Balakrishnar, Kelly Mok, Patsy Soon, André Franken, Hans Neubauer, Paul de Souza, Therese M. Becker

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Therapy of hormone receptor positive breast cancer (BCa) generally targets estrogen receptor (ER) function and signaling by reducing estrogen production or by blocking its interaction with the ER. Despite good long-term responses, resistance to treatment remains a significant issue, with approximately 40% of BCa patients developing resistance to ET. Mutations in the gene encoding ERα, ESR1, have been identified in BCa patients and are implicated as drivers of resistance and disease recurrence. Understanding the molecular consequences of these mutations on ER protein levels and its activity, which is tightly regulated, is vital. ER activity is in part controlled via its short protein half-life and therefore changes to its stability, either through mutations or alterations in pathways involved in protein stability, may play a role in therapy resistance. Understanding these connections and how ESR1 alterations could affect protein stability may identify novel biomarkers of resistance. This review explores the current reported data regarding posttranslational modifications (PTMs) of the ER and the potential impact of known resistance associated ESR1 mutations on ER regulation by affecting these PTMs in the context of ET resistance.
Original languageEnglish
Article number2077
Number of pages23
JournalCells
Volume9
Issue number9
DOIs
Publication statusPublished - 2020

Open Access - Access Right Statement

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Keywords

  • breast
  • cancer
  • hormone therapy
  • post, translational modification
  • proteasome

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