G protein-coupled receptor 30 is critical for a progestin-induced growth inhibition in MCF-7 breast cancer cells

Endocrinology. 2002 Sep;143(9):3376-84. doi: 10.1210/en.2001-211445.


The issue of how progesterone affects mammary gland growth is controversial, and the mechanism governing the effects of the hormone remains mostly unknown. We have previously shown that G protein-coupled receptor 30 (GPR30) is a progestin target gene whose expression correlates with progestin-induced growth inhibition in breast cancer cells. In this study, we investigate the role of GPR30 in regulating cell proliferation and mediating progestin-induced growth inhibition. When progestin failed to inhibit the growth of MCF-7 cells and instead stimulated growth, GPR30 was down-regulated. In this way, the inhibitory or stimulatory affects that progestin has on proliferation correlated with the level of expression of GPR30. Transient expression of GPR30 resulted in a marked inhibition of cell proliferation independent of estrogen treatment. GPR30 antisense was used to evaluate the role of GPR30 expression in progestin-induced growth inhibition. A diminished GPR30 mRNA expression by the antisense stimulated growth. Interestingly, GPR30 antisense abrogated the growth inhibitory effect of progestin and progesterone. Indeed, progestin induced 1) a reduction in cell proliferation, 2) G1-phase arrest, and 3) down-regulation of cyclin D1 was diminished. These data suggest that the orphan receptor, GPR30, is important for the inhibitory effect of progestin on growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Cycle / drug effects
  • Cell Division / drug effects*
  • Cyclin D1 / analysis
  • DNA / biosynthesis
  • Estradiol / pharmacology
  • Flow Cytometry
  • G1 Phase
  • Gene Expression
  • Humans
  • Medroxyprogesterone Acetate / pharmacology
  • Oligodeoxyribonucleotides, Antisense / genetics
  • Progestins / pharmacology*
  • RNA, Messenger / analysis
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled*
  • Receptors, Progesterone / drug effects
  • Receptors, Progesterone / physiology
  • Tetracycline / pharmacology
  • Transfection
  • Tumor Cells, Cultured


  • GPER1 protein, human
  • Oligodeoxyribonucleotides, Antisense
  • Progestins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • Receptors, Progesterone
  • Cyclin D1
  • Estradiol
  • DNA
  • Medroxyprogesterone Acetate
  • Tetracycline