Abstract B134: Stathmin is involved in the maternal embryonic leucine zipper kinase pathway in human astrocytomas.

Abstract

Introduction: Maternal Embryonic Leucine Zipper Kinase (MELK) is a serine/threonine kinase involved in several cell processes, including the cell cycle, proliferation, apoptosis and mRNA processing. MELK has shown multiple features consistent with the potential utility of this gene as an anticancer target, including in astrocytomas, the most common brain tumor in adults. Nevertheless the pathway of MELK in tumorigenesis is not well known yet. Purpose: This study aim to analyze genes and proteins involved in the MELK pathway in the tumorigenesis of gliomas, enabling the discovery of new therapeutic targets. Material and Methods: Analysis of the expression profile of a panel of protein relevant to the process of tumorigenesis that MELK is involved was performed by Proteomic analysis by two dimensional electrophoresis and mass spectrometry for human glioma cell line U87MG transfected with siRNA for the MELK compared to U87MG transfected with non-target control (NTC) cells. Analysis and validation of gene expression was performed by Quantitative real time PCR (qRT-PCR) using SYBR Green method in a series of 154 astrocytomas of different malignant grade (23 AGI, 26 AGII, 18 AGIII and 87 GBM) relative to 22 non neoplastic (NN) brain samples. Results: Differentially expressed proteins in U87MG cell line transfected with siRNA for the MELK compared to NTC control cells were identified by proteomic analysis. One of the proteins with lower expression when MELK was silenced was Stathmin (STMN1). The analysis in astrocytoma samples showed lower significant STMN1 relative expression of astrocytoma samples when compared to NN. Spearman correlation for gene expression levels of MELK and STMN1 for GBM samples were statistically significant (r=0.66, p<0.003). We found significant differences of median survival times of two GBM groups: 39 with hypoexpression of both STMN1 and MELK (8 months), versus 9 with hypoexpression of STMN1 and hiperexpression of MELK (5 months), log rank=0.016. Conclusions: STMN1 plays a role in regulation of the cell cycle and is defined as an oncoprotein. Thus, our results showed that STMN1 is involved in the MELK pathway suggesting that this protein plays an important role in glioma tumorigenesis. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B134. Citation Format: Miyuki Uno, Sueli Mieko Oba-Shinjo, Roseli Silva, Marcela Gimenez, Gisele Reis, Jose C. Rosa, Suely K. N. Marie. Stathmin is involved in the maternal embryonic leucine zipper kinase pathway in human astrocytomas. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B134.