Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells.
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.
Ahola
Tytti M
TM
Department of Cell Biology, Medical School, 33014 University of Tampere, Finland. ta55935@uta.fi
Purmonen
Sami
S
Pennanen
Pasi
P
Zhuang
Ya-Hua
YH
Tuohimaa
Pentti
P
Ylikomi
Timo
T
D001943:Breast Neoplasms / Q000378:metabolism*; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000235:genetics*; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C109584:GPER1 protein, human; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D017258:Medroxyprogesterone Acetate; D019204:GTP-Binding Proteins