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Conference Paper: Epigenetic inactivation of serine protease inhibitor TFPI-2 in human HCC

TitleEpigenetic inactivation of serine protease inhibitor TFPI-2 in human HCC
Authors
Issue Date2006
Citation
AACR 97th Annual Meeting, Washington, DC, 1–5 April 2006. In Cancer Research, 2006, v. 66 n. 8S, p. 382 Abstract no. 1618 How to Cite?
AbstractLiver cancer (hepatocellular carcinoma, HCC) is a prevalent cancer worldwide and is the second most common fatal cancer in Southeast Asia and Hong Kong. In liver cancer, tumor suppressor genes are known to play very important roles in carcinogenesis. Apart from deletions, epigenetic mechanisms such as aberrant promoter methylation and histone modification also significantly contribute to the inactivation of tumor suppressor genes. In this study, we used a high-throughput microarray technology to compare the changes of gene expression profiles of three HCC cell lines (Hep3B, SMMC-7721 and BEL-7402) after treatment by a global demethylating agent (5-aza-2’-deoxycytidine, 5-aza-2’-dC). By screening more than 15,000 genes, we identified a substantial number of genes with mRNA expression significantly restored after 5-aza-2’-dC treatment. About 300 transcripts were found to be upregulated in at least two of these three HCC cell lines. One of the candidate genes we identified with this approach is TFPI-2 (tissue-factor pathway inhibitor-2), a newly identified Kunitz-type serine protease inhibitor. TFPI-2 strongly inhibited the activity of trypsin, plasmin, and factor VIIa-tissue factor complex and was found to be suppresses cancer invasion both in vivo and in vitro. In this study, we aim at investigate the role of TFPI-2 in human HCC. We found that TFPI-2 mRNA expression was lower in HCC cell lines and was significantly upregulated with 5-Aza-dC treatment. Bisulfite DNA sequencing confirmed that the TFPI-2 promoter was hypermethylated in these HCC cell lines. In human HCC samples, with bisulfite DNA sequencing, we found that TFPI-2 promoter was hypermethylated in a subset of human HCCs. In addition, TFPI-2 mRNA expression was frequently downregulated in HCC by ≥2 folds, as compared with the corresponding non-tumorous livers. Our findings suggest that TFPI-2 was frequently inactivated in human HCC and epigenetic silencing of the TFPI-2 gene may contribute to human hepatocarcinogenesis. (This study was funded in part by Michael Kadoorie Cancer Genetic Research Program of the Kadoorie Charitable Foundation)
Persistent Identifierhttp://hdl.handle.net/10722/104499
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorWong, CMen_HK
dc.contributor.authorCheung, OFen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2010-09-25T21:55:34Z-
dc.date.available2010-09-25T21:55:34Z-
dc.date.issued2006en_HK
dc.identifier.citationAACR 97th Annual Meeting, Washington, DC, 1–5 April 2006. In Cancer Research, 2006, v. 66 n. 8S, p. 382 Abstract no. 1618-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/104499-
dc.description.abstractLiver cancer (hepatocellular carcinoma, HCC) is a prevalent cancer worldwide and is the second most common fatal cancer in Southeast Asia and Hong Kong. In liver cancer, tumor suppressor genes are known to play very important roles in carcinogenesis. Apart from deletions, epigenetic mechanisms such as aberrant promoter methylation and histone modification also significantly contribute to the inactivation of tumor suppressor genes. In this study, we used a high-throughput microarray technology to compare the changes of gene expression profiles of three HCC cell lines (Hep3B, SMMC-7721 and BEL-7402) after treatment by a global demethylating agent (5-aza-2’-deoxycytidine, 5-aza-2’-dC). By screening more than 15,000 genes, we identified a substantial number of genes with mRNA expression significantly restored after 5-aza-2’-dC treatment. About 300 transcripts were found to be upregulated in at least two of these three HCC cell lines. One of the candidate genes we identified with this approach is TFPI-2 (tissue-factor pathway inhibitor-2), a newly identified Kunitz-type serine protease inhibitor. TFPI-2 strongly inhibited the activity of trypsin, plasmin, and factor VIIa-tissue factor complex and was found to be suppresses cancer invasion both in vivo and in vitro. In this study, we aim at investigate the role of TFPI-2 in human HCC. We found that TFPI-2 mRNA expression was lower in HCC cell lines and was significantly upregulated with 5-Aza-dC treatment. Bisulfite DNA sequencing confirmed that the TFPI-2 promoter was hypermethylated in these HCC cell lines. In human HCC samples, with bisulfite DNA sequencing, we found that TFPI-2 promoter was hypermethylated in a subset of human HCCs. In addition, TFPI-2 mRNA expression was frequently downregulated in HCC by ≥2 folds, as compared with the corresponding non-tumorous livers. Our findings suggest that TFPI-2 was frequently inactivated in human HCC and epigenetic silencing of the TFPI-2 gene may contribute to human hepatocarcinogenesis. (This study was funded in part by Michael Kadoorie Cancer Genetic Research Program of the Kadoorie Charitable Foundation)-
dc.languageengen_HK
dc.relation.ispartofCancer Researchen_HK
dc.titleEpigenetic inactivation of serine protease inhibitor TFPI-2 in human HCCen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailWong, CM: jackwong@pathology.hku.hken_HK
dc.identifier.emailCheung, OF: oifung@hkucc.hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hkucc.hku.hken_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.identifier.hkuros113960en_HK

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