Consideration of GREB1 as a potential therapeutic target for hormone-responsive or endocrine-resistant cancers

Expert Opin Ther Targets. 2014 Sep;18(9):1065-76. doi: 10.1517/14728222.2014.936382. Epub 2014 Jul 5.

Abstract

Introduction: Steroid hormones increase the incidence and promote the progression of many types of cancer. Exogenous estrogens increase the risk of developing breast, ovarian and endometrial cancer and many breast cancers initially respond to estrogen deprivation. Although steroid hormone signaling has been extensively studied, the mechanisms of hormone-stimulated cancer growth have not yet been fully elucidated, limiting opportunities for novel approaches to therapeutic intervention.

Areas covered: This review examines growing evidence for the important role played by the steroid hormone-induced gene called GREB1, or growth regulation by estrogen in breast cancer 1. GREB1 is a critical mediator of both the estrogen-stimulated proliferation of breast cancer cells and the androgen-stimulated proliferation of prostate cancer cells.

Expert opinion: Although its exact function in the cascade of hormone action remains unclear, the ability of GREB1 to modulate tumor progression in models of breast, ovarian and prostate cancer renders this gene an excellent candidate for further consideration as a potential therapeutic target. Research examining the mechanism of GREB1 action will help to elucidate its role in proliferation and its potential contribution to endocrine resistance and will determine whether GREB1 interference may have therapeutic efficacy.

Keywords: cancer; estradiol; estrogen; estrogen receptor α; estrogen response element; growth regulation by estrogen in breast cancer 1; proliferation.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gonadal Steroid Hormones / metabolism
  • Humans
  • Male
  • Molecular Targeted Therapy
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / pathology

Substances

  • Antineoplastic Agents
  • GREB1 protein, human
  • Gonadal Steroid Hormones
  • Neoplasm Proteins