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Article: Down-regulation and promoter methylation of tissue inhibitor of metalloproteinase 3 in choriocarcinoma

TitleDown-regulation and promoter methylation of tissue inhibitor of metalloproteinase 3 in choriocarcinoma
Authors
KeywordsChoriocarcinoma
Methylation
TIMP3
Issue Date2004
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ygyno
Citation
Gynecologic Oncology, 2004, v. 94 n. 2, p. 375-382 How to Cite?
AbstractObjective. To assess the differential gene expression in neoplastic and normal trophoblastic cells and evaluate the effect of methylation on tissue inhibitor of metalloproteinase 3 (TIMP3) expression in choriocarcinoma (CCA) cells. Methods. The Atlas™ Human Cancer 1.2 Array (Clontech) was used to compare differential gene expression in a trophoblastic cell line (B6) established from first term placenta with two choriocarcinoma cell lines (JAR and JEG-3). The differentially expressed candidate genes in the placental and malignant trophoblastic cells in these cell lines were confirmed by real-time polymerase chain reaction (PCR), Western blotting and immunohistochemistry. Differential expression of a specific gene, TIMP3, was confirmed by immunohistochemistry using clinical specimens of choriocarcinoma and placenta. The involvement of promoter methylation in suppression of TIMP3 expression in choriocarcinoma was examined using methylation-specific PCR (MSP) and demethylation treatment. Results. Differential expression of 23 genes was observed in choriocarcinoma cell lines compared to the placental trophoblastic cells using the cDNA array analysis (Atlas™ Human Cancer Array, Clontech). Among these differentially expressed genes, down-regulation of TIMP3, PLAB, IGFBP3 and up-regulation of CCNB1 were confirmed by real-time PCR determination. Reduced expression of TIMP3 was further confirmed in clinical samples of choriocarcinoma by immunohistochemical staining. Methylation of TIMP3 promoter was detected in choriocarcinoma cell lines and clinical samples of choriocarcinoma. Treatment with a demethylation drug, 5-aza-2′- deoxycytidine, in choriocarcinoma cell lines restored TIMP3 expression. Conclusion. Down-regulation of TIMP3, PLAB, IGFBP3 and up-regulation of CCNB1 were observed in choriocarcinoma cells compared to placental trophoblasts. Down-regulation of TIMP3 expression was confirmed in clinical specimens of choriocarcinoma and may play a role in its pathogenesis. Promoter methylation of the TIMP3 is involved in suppression of TIMP3 expression. Differentiation expression of TIMP3 in choriocarcinoma may have potential application in clinical diagnosis and patient treatment. © 2004 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/67406
ISSN
2015 Impact Factor: 4.198
2015 SCImago Journal Rankings: 2.284
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorFeng, Hen_HK
dc.contributor.authorCheung, ANYen_HK
dc.contributor.authorXue, WCen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorWang, Xen_HK
dc.contributor.authorFu, Sen_HK
dc.contributor.authorWang, Qen_HK
dc.contributor.authorNgan, HYSen_HK
dc.contributor.authorTsao, SWen_HK
dc.date.accessioned2010-09-06T05:54:52Z-
dc.date.available2010-09-06T05:54:52Z-
dc.date.issued2004en_HK
dc.identifier.citationGynecologic Oncology, 2004, v. 94 n. 2, p. 375-382en_HK
dc.identifier.issn0090-8258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67406-
dc.description.abstractObjective. To assess the differential gene expression in neoplastic and normal trophoblastic cells and evaluate the effect of methylation on tissue inhibitor of metalloproteinase 3 (TIMP3) expression in choriocarcinoma (CCA) cells. Methods. The Atlas™ Human Cancer 1.2 Array (Clontech) was used to compare differential gene expression in a trophoblastic cell line (B6) established from first term placenta with two choriocarcinoma cell lines (JAR and JEG-3). The differentially expressed candidate genes in the placental and malignant trophoblastic cells in these cell lines were confirmed by real-time polymerase chain reaction (PCR), Western blotting and immunohistochemistry. Differential expression of a specific gene, TIMP3, was confirmed by immunohistochemistry using clinical specimens of choriocarcinoma and placenta. The involvement of promoter methylation in suppression of TIMP3 expression in choriocarcinoma was examined using methylation-specific PCR (MSP) and demethylation treatment. Results. Differential expression of 23 genes was observed in choriocarcinoma cell lines compared to the placental trophoblastic cells using the cDNA array analysis (Atlas™ Human Cancer Array, Clontech). Among these differentially expressed genes, down-regulation of TIMP3, PLAB, IGFBP3 and up-regulation of CCNB1 were confirmed by real-time PCR determination. Reduced expression of TIMP3 was further confirmed in clinical samples of choriocarcinoma by immunohistochemical staining. Methylation of TIMP3 promoter was detected in choriocarcinoma cell lines and clinical samples of choriocarcinoma. Treatment with a demethylation drug, 5-aza-2′- deoxycytidine, in choriocarcinoma cell lines restored TIMP3 expression. Conclusion. Down-regulation of TIMP3, PLAB, IGFBP3 and up-regulation of CCNB1 were observed in choriocarcinoma cells compared to placental trophoblasts. Down-regulation of TIMP3 expression was confirmed in clinical specimens of choriocarcinoma and may play a role in its pathogenesis. Promoter methylation of the TIMP3 is involved in suppression of TIMP3 expression. Differentiation expression of TIMP3 in choriocarcinoma may have potential application in clinical diagnosis and patient treatment. © 2004 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ygynoen_HK
dc.relation.ispartofGynecologic Oncologyen_HK
dc.subjectChoriocarcinomaen_HK
dc.subjectMethylationen_HK
dc.subjectTIMP3en_HK
dc.subject.meshCell Line, Tumor-
dc.subject.meshChoriocarcinoma - genetics - metabolism-
dc.subject.meshDNA Methylation-
dc.subject.meshTrophoblasts - metabolism - physiology-
dc.subject.meshUterine Neoplasms - genetics - metabolism-
dc.titleDown-regulation and promoter methylation of tissue inhibitor of metalloproteinase 3 in choriocarcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0090-8258&volume=94&issue=2&spage=375&epage=382&date=2004&atitle=Down-regulation+and+promoter+methylation+of+tissue+inhibitor+of+metalloproteinase+3+in+choriocarcinomaen_HK
dc.identifier.emailCheung, ANY:anycheun@hkucc.hku.hken_HK
dc.identifier.emailNgan, HYS:hysngan@hkucc.hku.hken_HK
dc.identifier.emailTsao, SW:gswtsao@hkucc.hku.hken_HK
dc.identifier.authorityCheung, ANY=rp00542en_HK
dc.identifier.authorityNgan, HYS=rp00346en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ygyno.2004.04.019en_HK
dc.identifier.pmid15297175-
dc.identifier.scopuseid_2-s2.0-3543087401en_HK
dc.identifier.hkuros92587en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-3543087401&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume94en_HK
dc.identifier.issue2en_HK
dc.identifier.spage375en_HK
dc.identifier.epage382en_HK
dc.identifier.isiWOS:000223303100019-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridFeng, H=7401736336en_HK
dc.identifier.scopusauthoridCheung, ANY=54927484100en_HK
dc.identifier.scopusauthoridXue, WC=7103165268en_HK
dc.identifier.scopusauthoridWang, Y=7601492022en_HK
dc.identifier.scopusauthoridWang, X=7501854829en_HK
dc.identifier.scopusauthoridFu, S=7402732420en_HK
dc.identifier.scopusauthoridWang, Q=35306290000en_HK
dc.identifier.scopusauthoridNgan, HYS=34571944100en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK

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