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Article: Adiponectin stimulates Wnt inhibitory factor-1 expression through epigenetic regulations involving the transcription factor specificity protein 1

TitleAdiponectin stimulates Wnt inhibitory factor-1 expression through epigenetic regulations involving the transcription factor specificity protein 1
Authors
Issue Date2008
PublisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/
Citation
Carcinogenesis, 2008, v. 29 n. 11, p. 2195-2202 How to Cite?
AbstractAdiponectin (ADN) is an adipokine possessing growth inhibitory activities against various types of cancer cells. Our previous results demonstrated that ADN could impede Wnt/beta-catenin-signaling pathways in MDA-MB-231 human breast carcinoma cells [Wang,Y. et al. (2006) Adiponectin modulates the glycogen synthase kinase-3 beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer Res., 66, 11462-11470]. Here, we extended our studies to elucidate the effects of ADN on regulating the expressions of Wnt inhibitory factor-1 (WIF1), a Wnt antagonist frequently silenced in human breast tumors. Our results showed that ADN time dependently stimulated WIF1 gene and protein expressions in MDA-MB-231 cells. Overexpression of WIF1 exerted similar inhibitory effects to those of ADN on cell proliferations, nuclear beta-catenin activities, cyclin D1 expressions and serum-induced phosphorylations of Akt and glycogen synthase kinase-3 beta. Blockage of WIF1 activities significantly attenuated the suppressive effects of ADN on MDA-MB-231 cell growth. Furthermore, our in vivo studies showed that both supplementation of recombinant ADN and adenovirus-mediated overexpression of this adipokine substantially enhanced WIF1 expressions in MDA-MB-231 tumors implanted in nude mice. More interestingly, we found that ADN could alleviate methylation of CpG islands located within the proximal promoter region of WIF1, possibly involving the specificity protein 1 (Sp1) transcription factor and its downstream target DNA methyltransferase 1 (DNMT1). Upon ADN treatment, the protein levels of both Sp1 and DNMT1 were significantly decreased. Using silencing RNA approaches, we confirmed that downregulation of Sp1 resulted in an increased expression of WIF1 and decreased methylation of WIF1 promoter. Taken together, these data suggest that ADN might elicit its antitumor activities at least partially through promoting WIF1 expressions. © The Author 2008. Published by Oxford University Press. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/163212
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.439
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLiu, Jen_HK
dc.contributor.authorLam, JBBen_HK
dc.contributor.authorChow, KHMen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorLam, KSLen_HK
dc.contributor.authorMoon, RTen_HK
dc.contributor.authorWang, Yen_HK
dc.date.accessioned2012-09-05T05:28:47Z-
dc.date.available2012-09-05T05:28:47Z-
dc.date.issued2008en_HK
dc.identifier.citationCarcinogenesis, 2008, v. 29 n. 11, p. 2195-2202en_HK
dc.identifier.issn0143-3334en_HK
dc.identifier.urihttp://hdl.handle.net/10722/163212-
dc.description.abstractAdiponectin (ADN) is an adipokine possessing growth inhibitory activities against various types of cancer cells. Our previous results demonstrated that ADN could impede Wnt/beta-catenin-signaling pathways in MDA-MB-231 human breast carcinoma cells [Wang,Y. et al. (2006) Adiponectin modulates the glycogen synthase kinase-3 beta/beta-catenin signaling pathway and attenuates mammary tumorigenesis of MDA-MB-231 cells in nude mice. Cancer Res., 66, 11462-11470]. Here, we extended our studies to elucidate the effects of ADN on regulating the expressions of Wnt inhibitory factor-1 (WIF1), a Wnt antagonist frequently silenced in human breast tumors. Our results showed that ADN time dependently stimulated WIF1 gene and protein expressions in MDA-MB-231 cells. Overexpression of WIF1 exerted similar inhibitory effects to those of ADN on cell proliferations, nuclear beta-catenin activities, cyclin D1 expressions and serum-induced phosphorylations of Akt and glycogen synthase kinase-3 beta. Blockage of WIF1 activities significantly attenuated the suppressive effects of ADN on MDA-MB-231 cell growth. Furthermore, our in vivo studies showed that both supplementation of recombinant ADN and adenovirus-mediated overexpression of this adipokine substantially enhanced WIF1 expressions in MDA-MB-231 tumors implanted in nude mice. More interestingly, we found that ADN could alleviate methylation of CpG islands located within the proximal promoter region of WIF1, possibly involving the specificity protein 1 (Sp1) transcription factor and its downstream target DNA methyltransferase 1 (DNMT1). Upon ADN treatment, the protein levels of both Sp1 and DNMT1 were significantly decreased. Using silencing RNA approaches, we confirmed that downregulation of Sp1 resulted in an increased expression of WIF1 and decreased methylation of WIF1 promoter. Taken together, these data suggest that ADN might elicit its antitumor activities at least partially through promoting WIF1 expressions. © The Author 2008. Published by Oxford University Press. All rights reserved.en_HK
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://carcin.oxfordjournals.org/en_HK
dc.relation.ispartofCarcinogenesisen_HK
dc.rightsCarcinogenesis . Copyright © Lippincott Williams & Wilkins.-
dc.subject.meshAdiponectin - Physiologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCpg Islandsen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshDna Primersen_US
dc.subject.meshEpigenesis, Geneticen_US
dc.subject.meshExtracellular Matrix Proteins - Geneticsen_US
dc.subject.meshGene Expression Regulation - Physiologyen_US
dc.subject.meshHumansen_US
dc.subject.meshIntercellular Signaling Peptides And Proteins - Geneticsen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred C57blen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshRna, Small Interferingen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshSp1 Transcription Factor - Physiologyen_US
dc.titleAdiponectin stimulates Wnt inhibitory factor-1 expression through epigenetic regulations involving the transcription factor specificity protein 1en_HK
dc.typeArticleen_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.emailLam, KSL: ksllam@hku.hken_HK
dc.identifier.emailWang, Y: yuwanghk@hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.identifier.authorityLam, KSL=rp00343en_HK
dc.identifier.authorityWang, Y=rp00239en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1093/carcin/bgn194en_HK
dc.identifier.pmid18701434-
dc.identifier.scopuseid_2-s2.0-56049102826en_HK
dc.identifier.hkuros154210-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-56049102826&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume29en_HK
dc.identifier.issue11en_HK
dc.identifier.spage2195en_HK
dc.identifier.epage2202en_HK
dc.identifier.isiWOS:000260977900021-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLiu, J=36066808300en_HK
dc.identifier.scopusauthoridLam, JBB=24448474900en_HK
dc.identifier.scopusauthoridChow, KHM=26430472800en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridLam, KSL=8082870600en_HK
dc.identifier.scopusauthoridMoon, RT=7202316413en_HK
dc.identifier.scopusauthoridWang, Y=34973733700en_HK

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