Suppression of G Protein-coupled Estrogen Receptor 1 (GPER1) Enhances the Anti-invasive Efficacy of Selective ERβ Agonists

Anticancer Res. 2022 Nov;42(11):5187-5194. doi: 10.21873/anticanres.16025.

Abstract

Background/aim: G protein-coupled estrogen receptor 1 (GPER1) is often over-expressed in triple negative breast cancer (TNBC). GPER1 is responsible for many of the non-genomic, membrane-initiated effects of estrogens. Therefore, we have analyzed the effects of GPER1 knockdown using specific siRNA.

Materials and methods: Transient GPER1 silencing was conducted using RNA interference and confirmed by RT-PCR and western blot. Viability of human breast cancer cell lines MDA-MB 231 and HCC 1806 was tested using AlamarBlue assay. Cell invasion was analyzed by assessment of cell migration rate through an artificial basement membrane in a modified Boyden chamber.

Results: Viability of both cell lines was slightly decreased after suppression of GPER1 expression. Knockdown of GPER1 resulted in a significantly reduced invasion of the TNBC cells. The anti-invasive effect of selective ERβ agonists was significantly stronger after knockdown of GPER1 expression. In addition, the efficacy of tamoxifen treatment was significantly increased after suppression of GPER1 expression.

Conclusion: Suppression of GPER1 reduced the metastatic behavior of TNBC cells, improved the anti-invasive efficacy of selective ERβ agonists and sensitized cells to 4OH-tamoxifen.

Keywords: Breast cancer; G protein-coupled estrogen receptor 1 (GPER1); invasion; selective ERβ agonists; tamoxifen resistance.

MeSH terms

  • Carcinoma, Hepatocellular*
  • Cell Line, Tumor
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / metabolism
  • Estrogens / pharmacology
  • GTP-Binding Proteins / metabolism
  • Humans
  • Liver Neoplasms*
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Tamoxifen / pharmacology
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • GTP-Binding Proteins
  • Receptors, G-Protein-Coupled
  • RNA, Small Interfering
  • Tamoxifen
  • GPER1 protein, human