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

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

Author Marie, Suely K. N. Google Scholar
Okamoto, Oswaldo Keith Autor UNIFESP Google Scholar
Uno, Miyuki Google Scholar
Hasegawa, Ana Paula G. Google Scholar
Oba-Shinjo, Sueli Mieko Autor UNIFESP Google Scholar
Cohen, Tzeela Google Scholar
Camargo, Anamaria A. Google Scholar
Kosoy, Ana Google Scholar
Carlotti, Carlos G. Google Scholar
Toledo, Silvia Regina Caminada de Autor UNIFESP Google Scholar
Moreira-Filho, Carlos A. Google Scholar
Zago, Marco A. Google Scholar
Simpson, Andrew J. Google Scholar
Caballero, Otavia L. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Mem Sloan Kettering Canc Ctr
Hosp Alemao Oswaldo Cruz
Albert Einstein Res & Educ Inst
Abstract We 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.
Keywords glioblastoma
pilocytic astrocytoma
molecular target
Language English
Date 2008-02-15
Published in International Journal of Cancer. Hoboken: Wiley-liss, v. 122, n. 4, p. 807-815, 2008.
ISSN 0020-7136 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 807-815
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000252522700014

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