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Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells
Tytti M Ahola1, Sami Purmonen, Pasi Pennanen
1Department of Cell Biology, Medical School, 33014 University of Tampere, Finland. ta55935@uta.fi
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.
Insights
Medroxyprogesterone acetate (MPA) upregulates G-protein-coupled receptor 30 (GPR30) in breast cancer cells, correlating with growth inhibition. This identifies GPR30 as a novel progestin target gene.
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Background:
- Medroxyprogesterone acetate (MPA) is a progestin used in hormone therapies.
- Gene expression changes are critical in understanding cancer cell growth.
- G-protein-coupled receptor 30 (GPR30) is implicated in various cellular processes.
Purpose of the Study:
- To identify genes regulated by MPA during growth inhibition.
- To investigate the role of GPR30 in progestin-induced effects on breast cancer cells.
- To explore the involvement of MAPK pathways in GPR30 regulation.
Main Methods:
- Differential display was employed to identify differentially expressed genes.
- Northern blot analysis was used to confirm GPR30 mRNA expression.
- MCF-7 and other breast cancer cell lines were treated with progestins and pathway inhibitors.
Main Results:
- MPA upregulated GPR30 mRNA in estrogen-treated MCF-7 cells.
- GPR30 is a progestin-specific target gene, upregulated by progesterone and abrogated by RU486.
- GPR30 upregulation correlated with MPA-induced growth inhibition across cell lines.
- GPR30 regulation was independent of ERK/ERK2 but influenced by p38 pathway inhibition.
Conclusions:
- GPR30 is a novel progestin target gene in breast cancer.
- GPR30 expression upregulation is linked to progestin-mediated growth inhibition.
- The p38 MAPK pathway may play a role in regulating GPR30 expression.