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Expression analysis of genes related to MELK pathway in astrocytomas


In order to discover new therapeutic targets, our research group selected hyperexpressed genes in glioblastomas (GBMs) compared to pilocytic astrocytoma (AGI) by microarray analysis. Among the selected genes, the gene called protein kinase MELK (Maternal Embryonic Leucine Zipper Kinase) showed a higher expression in GBMs compared to AGI. The increased expression of MELK was proportional to the degree of tumor confirmed by real-time PCR (qRT-PCR) in an extended series of astrocytomas. The result showed that glioma cells lines transfected with MELK-specific siRNA led to a reduction in the proliferation assays of anchorage independent growth and MTT when compared to controls. MELK was also observed that may be inhibiting apoptosis and is involved in the increase of cell migration in these tumors (Preliminary Results). The principal limitation of studies on the role of MELK as a protein kinase is the lack of knowledge of the processes or cell-signaling pathways in which they are involved. Due to the great potentiality of MELK as a therapeutic target, the continuity of this study is essential to the better understanding of the function that MELK is involved in tumorigenesis of astrocytomas. So, this project aims to analyze the profile the expression of a panel of genes relevant to the process of tumorigenesis (proliferation, migration, apoptosis) that MELK is involved by analysis of gene expression (qRT-PCR) using three RT2 Profiler PCR Arrays (Cancer Pathway Finder, Cell Motility Apoptosis Pathway) before and after stablished glioma cell lines transfected with MELK-specific siRNA. The study of protein expression will be performed by two dimensional electrophoresis by mass spectrometry. Validation of expression of relevant genes will be performed by qRT-PCR in a series of astrocytomas of different grades of malignancy astrocytomas. The expected results are to better understand the role of MELK and proteins involved in processes and signaling pathways in astrocytomas, which could lead to the discovery of new therapeutic targets. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
NAGAHASHI MARIE, SUELY KAZUE; OBA-SHINJO, SUELI MIEKO; DA SILVA, ROSELI; GIMENEZ, MARCELA; REIS, GISELE NUNES; TASSAN, JEAN-PIERRE; ROSA, JOSE CESAR; UNO, MIYUKI. Stathmin involvement in the maternal embryonic leucine zipper kinase pathway in glioblastoma. PROTEOME SCIENCE, v. 14, . (04/12133-6, 12/15896-7)

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