Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas Journal Article
| Authors: | Marie, S. K. N.; Okamoto, O. K.; Uno, M.; Hasegawa, A. P. G.; Oba-Shinjo, S. M.; Cohen, T.; Camargo, A. A.; Kosoy, A.; Carlotti, C. G. Jr; Toledo, S.; Moreira-Filho, C. A.; Zago, M. A.; Simpson, A. J.; Caballero, O. L. |
| Article Title: | Maternal embryonic leucine zipper kinase transcript abundance correlates with malignancy grade in human astrocytomas |
| 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, 1L13RA2 and K1AA0101 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. © 2007 Wiley-Liss, Inc. |
| Keywords: | adult; child; controlled study; human tissue; unclassified drug; human cell; methylation; promoter region; genetics; validation process; brain tumor; brain neoplasms; cancer grading; polymerase chain reaction; cell proliferation; mitosis; metabolism; gene overexpression; reverse transcription polymerase chain reaction; apoptosis; gene amplification; gene expression; gene expression profiling; small interfering rna; rna, small interfering; cancer cell culture; pathology; tumor cells, cultured; protein serine threonine kinase; dna methylation; central nervous system tumor; cancer invasion; gene expression regulation; oncogene; gene expression regulation, neoplastic; drug antagonism; cell culture; brain; reverse transcriptase polymerase chain reaction; oligonucleotide array sequence analysis; protein-serine-threonine kinases; glioblastoma; nucleotide sequence; medulloblastoma; dna microarray; microarray; gene dosage; cell cycle regulation; unindexed sequence; astrocytoma; phosphotransferase; anchorage independent growth; leucine zipper protein; pilocytic astrocytoma; promoter regions (genetics); melk; molecular target; maternal embryonic leucine zipper kinase; melk protein, human; aspm gene; aukb gene; il13ra2 gene; kiaa0i01 gene; melk gene; prc1 gene |
| Journal Title: | International Journal of Cancer |
| Volume: | 122 |
| Issue: | 4 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2008-02-15 |
| Start Page: | 807 |
| End Page: | 815 |
| Language: | English |
| DOI: | 10.1002/ijc.23189 |
| PUBMED: | 17960622 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 18" - "Export Date: 17 November 2011" - "CODEN: IJCNA" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work