Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells

Eur J Biochem. 2002 May;269(10):2485-90. doi: 10.1046/j.1432-1033.2002.02912.x.

Abstract

A differential display method was used to study genes the expression of which is altered during growth inhibition induced by medroxyprogesterone acetate (MPA). A transcript of G-protein-coupled receptor 30 (GPR30) was upregulated by MPA in estrogen-treated MCF-7 breast cancer cells. Northern-blot analysis showed a progestin-specific primary target gene, which was enhanced by progesterone and different progestins, but not by dihydrotestosterone or dexamethasone, and which was abrogated by antiprogestin RU486. The dose-dependent and time-dependent increase in GPR30 mRNA expression correlated with MPA-induced growth inhibition in MCF-7 cells. Additionally, GPR30 upregulation by progestin correlated with growth inhibition when a comparison was made between different breast cancer cell lines. The ERK1/ERK2 pathway is capable of inducing progesterone receptor-dependent and ligand-dependent transcription. Thus we sought to establish whether different MAPK pathway inhibitors affect progestin-induced GPR30 mRNA regulation. The regulation of GPR30 was independent of ERK pathway activation, but the p38 pathway inhibitor induced GPR30 expression, which suggested a potential gene regulation pathway. These data demonstrate a new progestin target gene, the expression of which correlates with growth inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Cloning, Molecular
  • GTP-Binding Proteins / metabolism
  • Gene Expression Profiling
  • Medroxyprogesterone Acetate / pharmacology*
  • Receptors, Cell Surface / genetics*
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled*
  • Tumor Cells, Cultured
  • Up-Regulation*

Substances

  • GPER1 protein, human
  • Receptors, Cell Surface
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • Medroxyprogesterone Acetate
  • GTP-Binding Proteins