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Article: Epigenetic dysregulation of Wnt signaling pathway in multiple myeloma

TitleEpigenetic dysregulation of Wnt signaling pathway in multiple myeloma
Authors
Issue Date2007
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leu
Citation
Leukemia, 2007, v. 21 n. 12, p. 2527-2536 How to Cite?
AbstractWnt signaling has recently been implicated in carcinogenesis. We studied the activity of Wnt signaling and the methylation status of WIF1, DKK3, APC, SFRP1, SFRP2, SFRP4 and SFRP5 by methylation-specific PCR in myeloma cell lines and primary myeloma samples. Of the four cell lines, Wnt signaling was constitutively activated in LP1 and WL2, correlating with hypermethylation and hence silencing. Moreover, 5-aza-2′-deoxycytidine treatment of these two cell lines showed progressive demethylation of methylated Wnt inhibitors, re-expression of transcripts and downregulation of Wnt signaling. In both LP1 and WL2 cells, multiple Wnts and Fzs were simultaneously expressed. Treatment of WL2, in which SFRP1 was completely methylated, with recombinant secreted Frizzled-related protein 1 (SFRP1) induced downregulation of Wnt signaling and inhibition of proliferation. In primary myeloma samples, 42% patients had methylation of at least one of these seven genes, of which 61.9% had ≥2 genes methylated. In conclusion, Wnt signaling is constitutively activated in myeloma, associated with methylation silencing of one or multiple soluble Wnt antagonists. An autocrine loop regulating Wnt signaling was demonstrated in the myeloma plasma cells, in which cellular proliferation was efficiently inhibited by recombinant SFRP1. Methylation study of a panel of genes, regulating a cellular pathway instead of isolated genes, is important.
Persistent Identifierhttp://hdl.handle.net/10722/77408
ISSN
2015 Impact Factor: 12.104
2015 SCImago Journal Rankings: 5.142
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChim, CSen_HK
dc.contributor.authorPang, Ren_HK
dc.contributor.authorFung, TKen_HK
dc.contributor.authorChoi, CLen_HK
dc.contributor.authorLiang, Ren_HK
dc.date.accessioned2010-09-06T07:31:34Z-
dc.date.available2010-09-06T07:31:34Z-
dc.date.issued2007en_HK
dc.identifier.citationLeukemia, 2007, v. 21 n. 12, p. 2527-2536en_HK
dc.identifier.issn0887-6924en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77408-
dc.description.abstractWnt signaling has recently been implicated in carcinogenesis. We studied the activity of Wnt signaling and the methylation status of WIF1, DKK3, APC, SFRP1, SFRP2, SFRP4 and SFRP5 by methylation-specific PCR in myeloma cell lines and primary myeloma samples. Of the four cell lines, Wnt signaling was constitutively activated in LP1 and WL2, correlating with hypermethylation and hence silencing. Moreover, 5-aza-2′-deoxycytidine treatment of these two cell lines showed progressive demethylation of methylated Wnt inhibitors, re-expression of transcripts and downregulation of Wnt signaling. In both LP1 and WL2 cells, multiple Wnts and Fzs were simultaneously expressed. Treatment of WL2, in which SFRP1 was completely methylated, with recombinant secreted Frizzled-related protein 1 (SFRP1) induced downregulation of Wnt signaling and inhibition of proliferation. In primary myeloma samples, 42% patients had methylation of at least one of these seven genes, of which 61.9% had ≥2 genes methylated. In conclusion, Wnt signaling is constitutively activated in myeloma, associated with methylation silencing of one or multiple soluble Wnt antagonists. An autocrine loop regulating Wnt signaling was demonstrated in the myeloma plasma cells, in which cellular proliferation was efficiently inhibited by recombinant SFRP1. Methylation study of a panel of genes, regulating a cellular pathway instead of isolated genes, is important.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/leuen_HK
dc.relation.ispartofLeukemiaen_HK
dc.subject.meshAdaptor Proteins, Signal Transducing - genetics - metabolismen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshAzacitidine - analogs & derivatives - pharmacologyen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshCell Line, Tumor - drug effects - metabolismen_HK
dc.subject.meshDNA Methylationen_HK
dc.subject.meshDNA, Neoplasm - chemistry - geneticsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Expression Regulation, Neoplastic - geneticsen_HK
dc.subject.meshGene Silencingen_HK
dc.subject.meshHumansen_HK
dc.subject.meshIntercellular Signaling Peptides and Proteins - genetics - metabolismen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshMultiple Myeloma - genetics - metabolism - pathologyen_HK
dc.subject.meshNeoplasm Proteins - genetics - physiologyen_HK
dc.subject.meshPhosphorylationen_HK
dc.subject.meshProtein Processing, Post-Translationalen_HK
dc.subject.meshRecombinant Proteins - pharmacologyen_HK
dc.subject.meshSignal Transduction - geneticsen_HK
dc.subject.meshWnt Proteins - physiologyen_HK
dc.subject.meshbeta Catenin - chemistryen_HK
dc.titleEpigenetic dysregulation of Wnt signaling pathway in multiple myelomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0887-6924&volume=21&spage=2527–2536&epage=&date=2007&atitle=Epigenetic+dysregulation+of+Wnt+signaling+pathway+in+multiple+myelomaen_HK
dc.identifier.emailChim, CS: jcschim@hku.hken_HK
dc.identifier.emailPang, R: robertap@hkucc.hku.hken_HK
dc.identifier.emailLiang, R: rliang@hku.hken_HK
dc.identifier.authorityChim, CS=rp00408en_HK
dc.identifier.authorityPang, R=rp00274en_HK
dc.identifier.authorityLiang, R=rp00345en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/sj.leu.2404939en_HK
dc.identifier.pmid17882284en_HK
dc.identifier.scopuseid_2-s2.0-36349013133en_HK
dc.identifier.hkuros147259en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36349013133&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume21en_HK
dc.identifier.issue12en_HK
dc.identifier.spage2527en_HK
dc.identifier.epage2536en_HK
dc.identifier.eissn1476-5551-
dc.identifier.isiWOS:000251139500018-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChim, CS=7004597253en_HK
dc.identifier.scopusauthoridPang, R=7004376659en_HK
dc.identifier.scopusauthoridFung, TK=7102715924en_HK
dc.identifier.scopusauthoridChoi, CL=8576533600en_HK
dc.identifier.scopusauthoridLiang, R=26643224900en_HK
dc.identifier.citeulike1679729-

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