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Conference Paper: Acquired temozolomide resistance in human malignant gliomas: a proteomics approach and the role of prolyl 4-hydroxylase, beta polypeptide

TitleAcquired temozolomide resistance in human malignant gliomas: a proteomics approach and the role of prolyl 4-hydroxylase, beta polypeptide
Authors
Issue Date2011
PublisherOxford University Press. The Journal's web site is located at http://neuro-oncology.oxfordjournals.org/
Citation
The 16th Annual Scientific Meeting of the Society for Neuro-Oncology in Conjunction with the AANS/CNS Section on Tumors, Orange County, California, USA, 17-20 November 2011. In Neuro-Oncology, 2011, v. 13 n. Suppl. 3, p. iii111, abstract no. ET-18 How to Cite?
Abstract
Temozolomide (TMZ) provides significant benefits in the treatment of malignant glioma, but many patients continue to suffer from progressive or recurrent disease because of the intrinsic or acquired resistance of their tumors to TMZ. In this study, we employed proteomic profiling to study changes in global protein expression in TMZ-resistant malignant glioma cells. We also investigated the potential role of one of the protein candidates, prolyl 4-hydroxylase, beta polypeptide (P4HB), that may be involved in the development of acquired TMZ resistance. Human malignant glioma cell lines (D54 and U87) with acquired TMZ resistance were first developed, and their biological behaviors were characterized before protein profiling analysis using 2-dimensional gel electrophoresis. Potential protein spot candidates were identified by MALDI-TOF/TOF. Transient transfection with small interfering RNAs was used to knock down potential candidates to study their biological roles. Our results revealed 15 protein spots that were highly upregulated or downregulated proteins in TMZ-resistant glioma cells. Among these, the protein P4HB was found to be consistently dysregulated in TMZ-resistant D54 sublines when compared to control sublines. Dysregulated expression of P4HB was also confirmed in U87 cells. Transient knockdown of P4HB expression was found to resensitize TMZ-resistant cells to subsequent treatment with TMZ. P4HB is known to play an important role in hypoxia-induced cell death. To our knowledge, this study is the first to describe the roles of P4HB in the regulation of TMZ-induced apoptosis in malignant glioma cells and in the development of acquired TMZ resistance. P4HB is a potential candidate for future investigations of TMZ-induced cytotoxicity and novel therapeutic strategies for the treatment of TMZ-resistant malignant glioma.
Persistent Identifierhttp://hdl.handle.net/10722/144582
ISSN
2013 Impact Factor: 5.286
2013 SCImago Journal Rankings: 3.023
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLeung, GKKen_US
dc.contributor.authorSun, Sen_US
dc.contributor.authorWong, STSen_US
dc.contributor.authorZhang, XQen_US
dc.contributor.authorPu, JKSen_US
dc.contributor.authorLui, WMen_US
dc.date.accessioned2012-02-03T06:15:02Z-
dc.date.available2012-02-03T06:15:02Z-
dc.date.issued2011en_US
dc.identifier.citationThe 16th Annual Scientific Meeting of the Society for Neuro-Oncology in Conjunction with the AANS/CNS Section on Tumors, Orange County, California, USA, 17-20 November 2011. In Neuro-Oncology, 2011, v. 13 n. Suppl. 3, p. iii111, abstract no. ET-18en_US
dc.identifier.issn1522-8517en_US
dc.identifier.urihttp://hdl.handle.net/10722/144582-
dc.description.abstractTemozolomide (TMZ) provides significant benefits in the treatment of malignant glioma, but many patients continue to suffer from progressive or recurrent disease because of the intrinsic or acquired resistance of their tumors to TMZ. In this study, we employed proteomic profiling to study changes in global protein expression in TMZ-resistant malignant glioma cells. We also investigated the potential role of one of the protein candidates, prolyl 4-hydroxylase, beta polypeptide (P4HB), that may be involved in the development of acquired TMZ resistance. Human malignant glioma cell lines (D54 and U87) with acquired TMZ resistance were first developed, and their biological behaviors were characterized before protein profiling analysis using 2-dimensional gel electrophoresis. Potential protein spot candidates were identified by MALDI-TOF/TOF. Transient transfection with small interfering RNAs was used to knock down potential candidates to study their biological roles. Our results revealed 15 protein spots that were highly upregulated or downregulated proteins in TMZ-resistant glioma cells. Among these, the protein P4HB was found to be consistently dysregulated in TMZ-resistant D54 sublines when compared to control sublines. Dysregulated expression of P4HB was also confirmed in U87 cells. Transient knockdown of P4HB expression was found to resensitize TMZ-resistant cells to subsequent treatment with TMZ. P4HB is known to play an important role in hypoxia-induced cell death. To our knowledge, this study is the first to describe the roles of P4HB in the regulation of TMZ-induced apoptosis in malignant glioma cells and in the development of acquired TMZ resistance. P4HB is a potential candidate for future investigations of TMZ-induced cytotoxicity and novel therapeutic strategies for the treatment of TMZ-resistant malignant glioma.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://neuro-oncology.oxfordjournals.org/en_US
dc.relation.ispartofNeuro-Oncologyen_US
dc.titleAcquired temozolomide resistance in human malignant gliomas: a proteomics approach and the role of prolyl 4-hydroxylase, beta polypeptideen_US
dc.typeConference_Paperen_US
dc.identifier.emailLeung, GKK: gilberto@hkucc.hku.hken_US
dc.identifier.emailSun, S: ssun@hku.hken_US
dc.identifier.emailWong, STS: thiansze@graduate.hku.hken_US
dc.identifier.emailLui, WM: mattlui@hku.hken_US
dc.identifier.authorityLeung, GKK=rp00522en_US
dc.identifier.authorityWong, STS=rp00478en_US
dc.identifier.doi10.1093/neuonc/nor158-
dc.identifier.pmcidPMC3222964-
dc.identifier.hkuros198206en_US
dc.identifier.hkuros204731-
dc.identifier.volume13en_US
dc.identifier.issueSuppl. 3en_US
dc.identifier.spageiii111-
dc.identifier.epageiii111-
dc.publisher.placeUnited States-
dc.description.otherThe 16th Annual Scientific Meeting of the Society for Neuro-Oncology in Conjunction with the AANS/CNS Section on Tumors, Orange County, California, USA, 17-20 November 2011. In Neuro-Oncology, 2011, v. 13 n. Suppl. 3, p. iii111, abstract no. ET-18-

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