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Article: Estrogen regulates snail and slug in the down-regulation of E-cadherin and induces metastatic potential of ovarian cancer cells through estrogen receptor α

TitleEstrogen regulates snail and slug in the down-regulation of E-cadherin and induces metastatic potential of ovarian cancer cells through estrogen receptor α
Authors
Issue Date2008
PublisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/
Citation
Molecular Endocrinology, 2008, v. 22 n. 9, p. 2085-2098 How to Cite?
AbstractTumorigenesis is a multistep process involving dysregulated cell growth and metastasis. Considerable evidence implicates a mitogenic action of estrogen in early ovarian carcinogenesis. In contrast, its influence in the metastatic cascade of ovarian tumor cells remains obscure. In the present study, we showed that 17β-estradiol (E2) increased the metastatic potential of human epithelial ovarian cancer cell lines. E2 treatment led to clear morphological changes characteristic of epithelial-mesenchymal transition (EMT) and an enhanced cell migratory propensity. These morphological and functional alterations were associated with changes in the abundance of EMT-related genes. Upon E2 stimulation, expression and promoter activity of the epithelial marker E-cadherin were strikingly suppressed, whereas EMT-associated transcription factors, Snail and Slug, were significantly up-regulated. This up-regulation was attributed to the increase in gene transcription activated by E2. Depletion of endogenous Snail or Slug using small interfering RNA (siRNA) attenuated E2-mediated decrease in E-cadherin. In addition, E2-induced cell migration was also neutralized by the siRNAs, suggesting that both transcription factors are indispensable for the prometastatic actions of E2. More importantly, by using selective estrogen receptor (ER) agonists, forced expression, and siRNA approaches, we identified that E2 triggered the metastatic behaviors exclusively through an ERα-dependent pathway. We also showed that ERβ had an opposing action on ERα because the presence of ERβ completely inhibited the EMT and down-regulation of E-cadherin induced by ERα. Collectively, this study provides a compelling argument that estrogen can potentiate tumor progression by EMT induction and highlights the crucial role of ERα in ovarian tumorigenesis. Copyright © 2008 by The Endocrine Society.
Persistent Identifierhttp://hdl.handle.net/10722/179072
ISSN
2015 Impact Factor: 3.432
2015 SCImago Journal Rankings: 2.195
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPark, SHen_US
dc.contributor.authorCheung, LWTen_US
dc.contributor.authorWong, ASTen_US
dc.contributor.authorLeung, PCKen_US
dc.date.accessioned2012-12-19T09:51:46Z-
dc.date.available2012-12-19T09:51:46Z-
dc.date.issued2008en_US
dc.identifier.citationMolecular Endocrinology, 2008, v. 22 n. 9, p. 2085-2098en_US
dc.identifier.issn0888-8809en_US
dc.identifier.urihttp://hdl.handle.net/10722/179072-
dc.description.abstractTumorigenesis is a multistep process involving dysregulated cell growth and metastasis. Considerable evidence implicates a mitogenic action of estrogen in early ovarian carcinogenesis. In contrast, its influence in the metastatic cascade of ovarian tumor cells remains obscure. In the present study, we showed that 17β-estradiol (E2) increased the metastatic potential of human epithelial ovarian cancer cell lines. E2 treatment led to clear morphological changes characteristic of epithelial-mesenchymal transition (EMT) and an enhanced cell migratory propensity. These morphological and functional alterations were associated with changes in the abundance of EMT-related genes. Upon E2 stimulation, expression and promoter activity of the epithelial marker E-cadherin were strikingly suppressed, whereas EMT-associated transcription factors, Snail and Slug, were significantly up-regulated. This up-regulation was attributed to the increase in gene transcription activated by E2. Depletion of endogenous Snail or Slug using small interfering RNA (siRNA) attenuated E2-mediated decrease in E-cadherin. In addition, E2-induced cell migration was also neutralized by the siRNAs, suggesting that both transcription factors are indispensable for the prometastatic actions of E2. More importantly, by using selective estrogen receptor (ER) agonists, forced expression, and siRNA approaches, we identified that E2 triggered the metastatic behaviors exclusively through an ERα-dependent pathway. We also showed that ERβ had an opposing action on ERα because the presence of ERβ completely inhibited the EMT and down-regulation of E-cadherin induced by ERα. Collectively, this study provides a compelling argument that estrogen can potentiate tumor progression by EMT induction and highlights the crucial role of ERα in ovarian tumorigenesis. Copyright © 2008 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.meshBase Sequenceen_US
dc.subject.meshCadherins - Genetics - Metabolismen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Movement - Drug Effectsen_US
dc.subject.meshDown-Regulation - Drug Effectsen_US
dc.subject.meshEstradiol - Pharmacologyen_US
dc.subject.meshEstrogen Receptor Alpha - Metabolismen_US
dc.subject.meshEstrogen Receptor Beta - Metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshOvarian Neoplasms - Genetics - Metabolism - Physiopathology - Secondaryen_US
dc.subject.meshPromoter Regions, Genetic - Drug Effectsen_US
dc.subject.meshRna, Small Interfering - Geneticsen_US
dc.subject.meshTranscription Factors - Antagonists & Inhibitors - Genetics - Metabolismen_US
dc.subject.meshUp-Regulation - Drug Effectsen_US
dc.titleEstrogen regulates snail and slug in the down-regulation of E-cadherin and induces metastatic potential of ovarian cancer cells through estrogen receptor αen_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.2007-0512en_US
dc.identifier.pmid18550773-
dc.identifier.scopuseid_2-s2.0-50649124650en_US
dc.identifier.hkuros152149-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-50649124650&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume22en_US
dc.identifier.issue9en_US
dc.identifier.spage2085en_US
dc.identifier.epage2098en_US
dc.identifier.isiWOS:000258856400008-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridPark, SH=7501831887en_US
dc.identifier.scopusauthoridCheung, LWT=14119560800en_US
dc.identifier.scopusauthoridWong, AST=23987963300en_US
dc.identifier.scopusauthoridLeung, PCK=55085135300en_US

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