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Article: Gonadotropin-induced apoptosis in human ovarian surface epithelial cells is associated with cyclooxygenase-2 up-regulation via the β-catenin/T-cell factor signaling pathway

TitleGonadotropin-induced apoptosis in human ovarian surface epithelial cells is associated with cyclooxygenase-2 up-regulation via the β-catenin/T-cell factor signaling pathway
Authors
Issue Date2006
PublisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/
Citation
Molecular Endocrinology, 2006, v. 20 n. 12, p. 3336-3350 How to Cite?
AbstractGonadotropins play a prominent role in ovarian function and pathology. We have shown that treatment with gonadotropins (FSH and LH/human chorionic gonadotropin) reduces the amount of N-cadherin with a concomitant induction of apoptosis in human ovarian surface epithelial (OSE) cells, but precise molecular mechanisms remain to be elucidated. Here, we demonstrated activation of β-catenin/T-cell factor (TCF) signaling by gonadotropins. We further showed that ectopic expression of N-cadherin was sufficient to recruit β-catenin to the plasma membrane, thereby blocking β-catenin/TCF-mediated transactivation in gonadotropin-treated cells. Transfection with β-catenin small interfering RNA or expression of dominant negative TCF inhibited apoptosis, whereas expression of dominant stable β-catenin (S37A) caused significant apoptosis, thus supporting a proapoptotic role for β-catenin/TCF in human OSE. In addition, we showed that gonadotropins enhanced β-catenin/TCF transcriptional activity through inactivation of glycogen synthase kinase-3β in a phosphatidylinositol 3-kinase/Akt- dependent manner, indicating cross talk between the phosphatidylinositol 3-kinase/Akt and β-catenin signaling pathways through glycogen synthase kinase-3β. Furthermore, gonadotropins increased cyclooxygenase-2 (COX-2) expression via the β-catenin/TCF pathway. COX-2 also played a role in gonadotropin-induced apoptosis, as treatment with the COX-2-specific inhibitor NS-398 or COX-2 small interfering RNA blocked gonadotropin-dependent apoptotic activity. These findings suggest that the participation of β-catenin in adhesion and signaling may represent a novel mechanism through which gonadotropins may regulate the cellular fate of human OSE. Copyright © 2006 by The Endocrine Society.
Persistent Identifierhttp://hdl.handle.net/10722/178970
ISSN
2015 Impact Factor: 3.432
2015 SCImago Journal Rankings: 2.195
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYuen, LPen_US
dc.contributor.authorWong, ASTen_US
dc.date.accessioned2012-12-19T09:51:09Z-
dc.date.available2012-12-19T09:51:09Z-
dc.date.issued2006en_US
dc.identifier.citationMolecular Endocrinology, 2006, v. 20 n. 12, p. 3336-3350en_US
dc.identifier.issn0888-8809en_US
dc.identifier.urihttp://hdl.handle.net/10722/178970-
dc.description.abstractGonadotropins play a prominent role in ovarian function and pathology. We have shown that treatment with gonadotropins (FSH and LH/human chorionic gonadotropin) reduces the amount of N-cadherin with a concomitant induction of apoptosis in human ovarian surface epithelial (OSE) cells, but precise molecular mechanisms remain to be elucidated. Here, we demonstrated activation of β-catenin/T-cell factor (TCF) signaling by gonadotropins. We further showed that ectopic expression of N-cadherin was sufficient to recruit β-catenin to the plasma membrane, thereby blocking β-catenin/TCF-mediated transactivation in gonadotropin-treated cells. Transfection with β-catenin small interfering RNA or expression of dominant negative TCF inhibited apoptosis, whereas expression of dominant stable β-catenin (S37A) caused significant apoptosis, thus supporting a proapoptotic role for β-catenin/TCF in human OSE. In addition, we showed that gonadotropins enhanced β-catenin/TCF transcriptional activity through inactivation of glycogen synthase kinase-3β in a phosphatidylinositol 3-kinase/Akt- dependent manner, indicating cross talk between the phosphatidylinositol 3-kinase/Akt and β-catenin signaling pathways through glycogen synthase kinase-3β. Furthermore, gonadotropins increased cyclooxygenase-2 (COX-2) expression via the β-catenin/TCF pathway. COX-2 also played a role in gonadotropin-induced apoptosis, as treatment with the COX-2-specific inhibitor NS-398 or COX-2 small interfering RNA blocked gonadotropin-dependent apoptotic activity. These findings suggest that the participation of β-catenin in adhesion and signaling may represent a novel mechanism through which gonadotropins may regulate the cellular fate of human OSE. Copyright © 2006 by The Endocrine Society.en_US
dc.languageengen_US
dc.publisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/en_US
dc.relation.ispartofMolecular Endocrinologyen_US
dc.rightsMolecular Endocrinology. Copyright © The Endocrine Society.-
dc.subject.meshApoptosisen_US
dc.subject.meshCell Adhesionen_US
dc.subject.meshCyclooxygenase 2 - Physiologyen_US
dc.subject.meshEpithelial Cells - Drug Effects - Enzymologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGlycogen Synthase Kinase 3 - Metabolismen_US
dc.subject.meshGonadotropins - Pharmacologyen_US
dc.subject.meshHumansen_US
dc.subject.meshMembrane Proteins - Agonists - Antagonists & Inhibitors - Physiologyen_US
dc.subject.meshOvary - Cytology - Drug Effects - Enzymologyen_US
dc.subject.meshPhosphatidylinositol 3-Kinases - Metabolismen_US
dc.subject.meshPhosphorylationen_US
dc.subject.meshProto-Oncogene Proteins C-Akt - Metabolismen_US
dc.subject.meshRna, Small Interfering - Genetics - Pharmacologyen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshTcf Transcription Factors - Agonists - Genetics - Physiologyen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.subject.meshUp-Regulationen_US
dc.subject.meshBeta Catenin - Agonists - Genetics - Physiologyen_US
dc.titleGonadotropin-induced apoptosis in human ovarian surface epithelial cells is associated with cyclooxygenase-2 up-regulation via the β-catenin/T-cell factor signaling pathwayen_US
dc.typeArticleen_US
dc.identifier.emailWong, AST: awong1@hkucc.hku.hken_US
dc.identifier.authorityWong, AST=rp00805en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1210/me.2006-0125en_US
dc.identifier.pmid16945989-
dc.identifier.scopuseid_2-s2.0-33751513321en_US
dc.identifier.hkuros130197-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33751513321&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume20en_US
dc.identifier.issue12en_US
dc.identifier.spage3336en_US
dc.identifier.epage3350en_US
dc.identifier.isiWOS:000242340400023-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYuen, LP=15081685200en_US
dc.identifier.scopusauthoridWong, AST=23987963300en_US

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