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Molecular regulation of estrogen receptors and recent advances on ERα36 splice variant in prostate cancer

Deborah Simão Souza1, Camila Rebelo Morgado Costa1, Larissa Thainá Brito Dias1

  • 1Laboratory of Experimental Endocrinology, Department of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04039-032, Brazil.

Journal of the Endocrine Society
|August 20, 2026
PubMed

Insights

Estrogen receptors (ERα, ERβ) and GPER are present in normal and cancerous prostate tissues. Their role in prostate cancer progression and treatment resistance requires further investigation, especially for variants like ERα36.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Prostate cancer is a leading cause of cancer death in men globally.
  • Current treatments for metastatic prostate cancer include androgen deprivation therapy, androgen receptor pathway inhibitors, and chemotherapy.
  • Therapeutic resistance and progression to castration-resistant prostate cancer remain significant clinical challenges.

Purpose of the Study:

  • To review existing and new evidence on estrogen receptor (ER) expression and function in the prostate.
  • To investigate the roles of ERα, ERβ, their variants, and G protein-coupled estrogen receptor (GPER) in normal and cancerous prostate tissues.
  • To highlight the need for targeted therapies against ER variants in prostate cancer.

Main Methods:

  • Literature review of published studies on ER and GPER expression and function.
  • Analysis of evidence from normal prostate gland, development, adulthood, and prostate cancer cell lines.
  • Examination of data from in vitro and xenograft models of castration-resistant prostate cancer (PC-3 and DU-145 cells).

Main Results:

  • Estrogen receptors (ERα, ERβ) and GPER are expressed in a cell-specific manner in the normal prostate gland.
  • ERα, ERβ, and GPER are present at transcript and protein levels in castration-resistant prostate cancer cell lines (PC-3, DU-145).
  • The ERα36 splice variant was detected in prostate cancer cells.

Conclusions:

  • Estrogen receptors and GPER are present in prostate cancer, suggesting potential roles in disease progression.
  • The functional significance of ER variants, such as ERα36, in prostate cancer requires further elucidation.
  • Development of selective inhibitors for ER variants is crucial for understanding their biology and therapeutic potential in prostate cancer.
Keywords:
ERα36 splice variantestrogen receptorprostate cancer cells

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