Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas

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dc.contributor.authorMarie, Suely K. N.
dc.contributor.authorOkamoto, Oswaldo Keith [UNIFESP]
dc.contributor.authorUno, Miyuki
dc.contributor.authorHasegawa, Ana Paula G.
dc.contributor.authorOba-Shinjo, Sueli Mieko [UNIFESP]
dc.contributor.authorCohen, Tzeela
dc.contributor.authorCamargo, Anamaria A.
dc.contributor.authorKosoy, Ana
dc.contributor.authorCarlotti, Carlos G.
dc.contributor.authorToledo, Silvia Regina Caminada de [UNIFESP]
dc.contributor.authorMoreira-Filho, Carlos A.
dc.contributor.authorZago, Marco A.
dc.contributor.authorSimpson, Andrew J.
dc.contributor.authorCaballero, Otavia L.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionMem Sloan Kettering Canc Ctr
dc.contributor.institutionHosp Alemao Oswaldo Cruz
dc.contributor.institutionAlbert Einstein Res & Educ Inst
dc.date.accessioned2016-01-24T13:49:34Z
dc.date.available2016-01-24T13:49:34Z
dc.date.issued2008-02-15
dc.description.abstractWe have performed cDNA microarray analyses to identify gene expression differences between highly invasive glioblastoma multiforme (GBM) and typically benign pilocytic astrocytomas (PA). Despite the significant clinical and pathological differences between the 2 tumor types, only 63 genes were found to exhibit 2-fold or greater overexpression in GBM as compared to PA. Forty percent of these genes are related to the regulation of the cell cycle and mitosis. QT-PCR validation of 6 overexpressed genes: MELK, AUKB, ASPM, PRC1, IL13RA2 and KIAA0101 confirmed at least a 5-fold increase in the average expression levels in GBM. Maternal embryonic leucine zipper kinase (MELK) exhibited the most statistically significant difference. A more detailed investigation of MELK expression was undertaken to study its oncogenic relevance. in the examination of more than 100 tumors of the central nervous system, we found progressively higher expression of MELK with astrocytoma grade and a noteworthy uniformity of high level expression in GBM. Similar level of overexpression was also observed in medulloblastoma. We found neither gene promoter hypomethylation nor amplification to be a factor in MELK expression, but were able to demonstrate that MELK knockdown in malignant astrocytoma cell lines caused a reduction in proliferation and anchorage-independent growth in in vitro assays. Our results indicate that GBM and PA differ by the expression of surprisingly few genes. Among them, MELK correlated with malignancy grade in astrocytomas and represents a therapeutic target for the management of the most frequent brain tumors in adult and children. (C) 2007 Wiley-Liss, Inc.en
dc.description.affiliationUniv São Paulo, Sch Med, Dept Neurol, BR-01246903 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Neurol & Neurosurg, São Paulo, Brazil
dc.description.affiliationMem Sloan Kettering Canc Ctr, New York Branch, Ludwig Inst Canc Res, New York, NY 10021 USA
dc.description.affiliationHosp Alemao Oswaldo Cruz, São Paulo Branch, Ludwig Inst Canc Res, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Sch Med, Div Neurosurg, Dept Surg, Ribeirao Preto, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Pediat Oncol Inst, Dept Pediat, São Paulo, Brazil
dc.description.affiliationAlbert Einstein Res & Educ Inst, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Sch Med, Dept Clin Med, Ribeirao Preto, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Neurol & Neurosurg, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Pediat Oncol Inst, Dept Pediat, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent807-815
dc.identifierhttp://dx.doi.org/10.1002/ijc.23189
dc.identifier.citationInternational Journal of Cancer. Hoboken: Wiley-liss, v. 122, n. 4, p. 807-815, 2008.
dc.identifier.doi10.1002/ijc.23189
dc.identifier.issn0020-7136
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/30445
dc.identifier.wosWOS:000252522700014
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofInternational Journal of Cancer
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectglioblastomaen
dc.subjectpilocytic astrocytomaen
dc.subjectmicroarrayen
dc.subjectMELKen
dc.subjectmolecular targeten
dc.titleMaternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomasen
dc.typeinfo:eu-repo/semantics/article
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