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Conference Paper: Overexpression of the histone methyltransferase enhancer of zeste homolog 2 was involved in multistep hepatocarcinogenesis and metastasis of hepatocellular carcinoma

TitleOverexpression of the histone methyltransferase enhancer of zeste homolog 2 was involved in multistep hepatocarcinogenesis and metastasis of hepatocellular carcinoma
Authors
Issue Date2009
PublisherAmerican Association for Cancer Research.
Citation
The 100th AACR Annual Meeting, Denver, CO., 18-22 April 2009. In Cancer Research, 2009, v. 69 n. 9S, Abstract no. 491 How to Cite?
AbstractBackground: Post-translational modifications on histone N-terminal tails are tightly associated with gene transcription regulation. Accumulating evidence has suggested that aberrant histone modifications are implicated in malignancy development. However, the roles and mechanisms of aberrant histone modifications in the development of hepatocellular carcinoma (HCC) are still warranted. In a pilot study, we observed that Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase specific for H3K27, was frequently deregulated in human HCC. The purpose of this present study is to investigate the role of EZH2 in hepatocarcinogenesis. Experimental Design: The expression of EZH2 mRNA and protein in primary HCC and corresponding non-tumorous livers were determined by real-time quantitative RT-PCR and immunohistochemistry, respectively. Clinicopathological analysis was also done to correlate EZH2 overexpression with clinicopathological parameters of HCC patients. Ectopic overexpression and RNA interference knockdown approaches were employed to study the functional implication of EZH2 in HCC cell lines. Results: Real-time quantitative RT-PCR was performed in 59 pairs of primary HCC samples and overexpression of EZH2 mRNA was found in 70% of primary HCC. Immunohistochemistry study of tissue microarrays consisted of 108 pairs of primary HCC also revealed that both number of positive cells and the intensity of EZH2 nuclear staining were significantly higher in primary HCC than their corresponding non-tumorous livers. Ectopic overexpression of EZH2 significantly increased the H3K27 trimethylation level in HCC cell lines. We also found that the expression level of EZH2 exhibited a stepwise increase along the multistep hepatocarcinogenesis, suggesting that overexpression of EZH2 may contribute to HCC progression. Furthermore, overexpression of EZH2 in HCC was significantly associated with aggressive tumor behaviors in HCC patients including the presence of venous invasion (p=0.043) and liver invasion (p=0.014), and the absence of tumor encapsulation (p=0.043). Consistently, knockdown of EZH2 by small interfering RNA suppressed migration of HCC cell lines, suggesting that upregulated EZH2 may contribute to the HCC metastasis. Conclusions: Our findings indicated that EZH2 was frequently upregulated in human HCC and was associated with HCC progression as well as the metastatic phenotypes.
Persistent Identifierhttp://hdl.handle.net/10722/153107
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorAu, SLKen_US
dc.contributor.authorWong, CCLen_US
dc.contributor.authorLee, JMFen_US
dc.contributor.authorWong, CMen_US
dc.contributor.authorNg, IOLen_US
dc.date.accessioned2012-07-16T09:56:53Z-
dc.date.available2012-07-16T09:56:53Z-
dc.date.issued2009en_US
dc.identifier.citationThe 100th AACR Annual Meeting, Denver, CO., 18-22 April 2009. In Cancer Research, 2009, v. 69 n. 9S, Abstract no. 491en_US
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/153107-
dc.description.abstractBackground: Post-translational modifications on histone N-terminal tails are tightly associated with gene transcription regulation. Accumulating evidence has suggested that aberrant histone modifications are implicated in malignancy development. However, the roles and mechanisms of aberrant histone modifications in the development of hepatocellular carcinoma (HCC) are still warranted. In a pilot study, we observed that Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase specific for H3K27, was frequently deregulated in human HCC. The purpose of this present study is to investigate the role of EZH2 in hepatocarcinogenesis. Experimental Design: The expression of EZH2 mRNA and protein in primary HCC and corresponding non-tumorous livers were determined by real-time quantitative RT-PCR and immunohistochemistry, respectively. Clinicopathological analysis was also done to correlate EZH2 overexpression with clinicopathological parameters of HCC patients. Ectopic overexpression and RNA interference knockdown approaches were employed to study the functional implication of EZH2 in HCC cell lines. Results: Real-time quantitative RT-PCR was performed in 59 pairs of primary HCC samples and overexpression of EZH2 mRNA was found in 70% of primary HCC. Immunohistochemistry study of tissue microarrays consisted of 108 pairs of primary HCC also revealed that both number of positive cells and the intensity of EZH2 nuclear staining were significantly higher in primary HCC than their corresponding non-tumorous livers. Ectopic overexpression of EZH2 significantly increased the H3K27 trimethylation level in HCC cell lines. We also found that the expression level of EZH2 exhibited a stepwise increase along the multistep hepatocarcinogenesis, suggesting that overexpression of EZH2 may contribute to HCC progression. Furthermore, overexpression of EZH2 in HCC was significantly associated with aggressive tumor behaviors in HCC patients including the presence of venous invasion (p=0.043) and liver invasion (p=0.014), and the absence of tumor encapsulation (p=0.043). Consistently, knockdown of EZH2 by small interfering RNA suppressed migration of HCC cell lines, suggesting that upregulated EZH2 may contribute to the HCC metastasis. Conclusions: Our findings indicated that EZH2 was frequently upregulated in human HCC and was associated with HCC progression as well as the metastatic phenotypes.-
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research.-
dc.relation.ispartofCancer Researchen_US
dc.titleOverexpression of the histone methyltransferase enhancer of zeste homolog 2 was involved in multistep hepatocarcinogenesis and metastasis of hepatocellular carcinomaen_US
dc.typeConference_Paperen_US
dc.identifier.emailAu, SLK: ausandy@hku.hken_US
dc.identifier.emailWong, CCL: carmencl@pathology.hku.hken_US
dc.identifier.emailLee, JMF: joyce@pathology.hku.hken_US
dc.identifier.emailWong, CM: jackwong@pathology.hku.hken_US
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.identifier.authorityWong, CCL=rp01602en_US
dc.identifier.authorityWong, CM=rp00231en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros155432en_US
dc.identifier.hkuros201644-
dc.publisher.placeUnited States-
dc.description.otherThe 100th Annual Meeting of the American Association for Cancer Research (AACR 2009), San Diego, CA., 18-22 April 2009. In Proceedings of AACR 2009, abstract no. 491-

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