Anticancer or carcinogenic? The role of estrogen receptor β in breast cancer progression

Pharmacol Ther. 2023 Feb:242:108350. doi: 10.1016/j.pharmthera.2023.108350. Epub 2023 Jan 20.

Abstract

Estrogen receptor β (ERβ) is closely related to breast cancer (BC) progression. Traditional concepts regard ERβ as a tumor suppressor. As studies show the carcinogenic effect of ERβ, some people have come to a new conclusion that ERβ serves as a tumor suppressor in estrogen receptor α (ERα)-positive breast cancer, while it is a carcinogen in ERα-negative breast cancer. However, we re-examine the role of ERβ and find this conclusion to be misleading based on the last decade's research. A large number of studies have shown that ERβ plays an anticancer role in both ERα-positive and ERα-negative breast cancers, and its carcinogenicity does not depend solely on the presence of ERα. Herein, we review the anticancer and oncogenic effects of ERβ on breast cancer progression in the past ten years, discuss the mechanism respectively, analyze the main reasons for the inconsistency and update ERβ selective ligand library. We believe a detailed and continuously updated review will help correct the one-sided understanding of ERβ, promoting ERβ-targeted breast cancer therapy.

Keywords: Bi-faced effect; Breast cancer; ERβ selective ligands; Estrogen receptor β; Mechanism study; cancer therapeutics.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Carcinogenesis
  • Carcinogens
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Female
  • Humans
  • Triple Negative Breast Neoplasms*

Substances

  • Carcinogens
  • Estrogen Receptor alpha
  • Estrogen Receptor beta