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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
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TitleAcquired temozolomide resistance in human malignant gliomas: a proteomics approach and the role of prolyl 4-hydroxylase, beta polypeptide
 
AuthorsLeung, GKK
Sun, S
Wong, STS
Zhang, XQ
Pu, JKS
Lui, WM
 
Issue Date2011
 
PublisherOxford University Press. The Journal's web site is located at http://neuro-oncology.oxfordjournals.org/
 
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-18 [How to Cite?]
DOI: http://dx.doi.org/10.1093/neuonc/nor158
 
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.
 
ISSN1522-8517
2013 Impact Factor: 5.286
2013 SCImago Journal Rankings: 3.023
 
DOIhttp://dx.doi.org/10.1093/neuonc/nor158
 
PubMed Central IDPMC3222964
 
DC FieldValue
dc.contributor.authorLeung, GKK
 
dc.contributor.authorSun, S
 
dc.contributor.authorWong, STS
 
dc.contributor.authorZhang, XQ
 
dc.contributor.authorPu, JKS
 
dc.contributor.authorLui, WM
 
dc.date.accessioned2012-02-03T06:15:02Z
 
dc.date.available2012-02-03T06:15:02Z
 
dc.date.issued2011
 
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.
 
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
 
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-18 [How to Cite?]
DOI: http://dx.doi.org/10.1093/neuonc/nor158
 
dc.identifier.doihttp://dx.doi.org/10.1093/neuonc/nor158
 
dc.identifier.epageiii111
 
dc.identifier.hkuros198206
 
dc.identifier.hkuros204731
 
dc.identifier.issn1522-8517
2013 Impact Factor: 5.286
2013 SCImago Journal Rankings: 3.023
 
dc.identifier.issueSuppl. 3
 
dc.identifier.pmcidPMC3222964
 
dc.identifier.spageiii111
 
dc.identifier.urihttp://hdl.handle.net/10722/144582
 
dc.identifier.volume13
 
dc.languageeng
 
dc.publisherOxford University Press. The Journal's web site is located at http://neuro-oncology.oxfordjournals.org/
 
dc.publisher.placeUnited States
 
dc.relation.ispartofNeuro-Oncology
 
dc.titleAcquired temozolomide resistance in human malignant gliomas: a proteomics approach and the role of prolyl 4-hydroxylase, beta polypeptide
 
dc.typeConference_Paper
 
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