| Grant number: | 12/15896-7 |
| Support Opportunities: | Regular Research Grants |
| Start date: | December 01, 2012 |
| End date: | November 30, 2014 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Miyuki Uno |
| Grantee: | Miyuki Uno |
| Host Institution: | Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
| Associated researchers: | Helder Picarelli ; José César Rosa ; Manoel Jacobsen Teixeira ; Roseli da Silva Soares ; Sueli Mieko Oba Shinjo ; Suely Kazue Nagahashi Marie |
Abstract
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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