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Progestin and G protein-coupled receptor 30 inhibit mitogen-activated protein kinase activity in MCF-7 breast cancer cells.
- Source :
-
Endocrinology [Endocrinology] 2002 Dec; Vol. 143 (12), pp. 4620-6. - Publication Year :
- 2002
-
Abstract
- We have previously shown that the G protein-coupled receptor (GPR)30 is critical for progestin-induced growth inhibition. In this study, we addressed signal transduction pathways involved in progestin-mediated signaling. Progestin could not provide any additional growth inhibitory effect to MCF-7 cells treated with specific MAPK kinase inhibitors, PD98059 and U0126. Medroxyprogesteroneacetate (MPA) induced a late (22-23 h) decrease in ERK-1 and -2 activities verified by immunoblotting and kinase assay. The inactivation was abrogated by antiprogestin. Transient expression of GPR30 decreased ERK-1 and -2 activity; and in the cells in which GPR30 expression was decreased by the antisense, ERK activities were increased. The antisense-expressing cells were able to significantly resist the growth-inhibitory effect of the MAPK kinase inhibitors PD98059 and U0126 but not that of other factors tested. Interestingly, the decrease of ERK activity induced by MPA was abrogated by GPR30 antisense. Collectively, these results show that MAPK activity is inhibited by progestin and GPR30 and suggest that progestin-induced ERK inactivation is mediated through GPR30. Coupled with our previous findings, the data imply that up-regulation of GPR30 by progestin leads to ERK-1 and -2 inactivation associated with MPA-induced growth inhibition.
- Subjects :
- Breast Neoplasms pathology
Butadienes pharmacology
Cell Division
DNA, Antisense genetics
Flavonoids pharmacology
Gene Expression
Humans
Medroxyprogesterone Acetate pharmacology
Mitogen-Activated Protein Kinase 1 antagonists & inhibitors
Mitogen-Activated Protein Kinase 3
Nitriles pharmacology
Receptors, Cell Surface genetics
Receptors, Estrogen
Signal Transduction
Tumor Cells, Cultured
Breast Neoplasms enzymology
Enzyme Inhibitors pharmacology
GTP-Binding Proteins physiology
Mitogen-Activated Protein Kinases antagonists & inhibitors
Progestins pharmacology
Receptors, Cell Surface physiology
Receptors, G-Protein-Coupled
Subjects
Details
- Language :
- English
- ISSN :
- 0013-7227
- Volume :
- 143
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 12446589
- Full Text :
- https://doi.org/10.1210/en.2002-220492