title: Stathmin involvement in the maternal embryonic leucine zipper kinase pathway in glioblastoma.
abstract: BACKGROUND
  Maternal Embryonic Leucine Zipper Kinase (MELK) is a serine/threonine kinase involved in cell cycle, differentiation, proliferation, and apoptosis. These multiple features are consistent with it being a potential anticancer target. Nevertheless, the MELK pathway in tumorigenesis is not yet completely understood. This study aims to identify proteins associated with MELK pathway in astrocytomas. To this end, proteomic data of the human glioma cell line U87MG transfected with siRNA for MELK were compared with non-target transfected control cells and compared with oligonucleotide microarray data.
  
  
  RESULTS
  In both assays, we identified stathmin/oncoprotein 18 (STMN1), involved in cell cycle. STMN1 gene expression was further assessed in a series of 154 astrocytomas and 22 non-neoplastic brain samples by qRT-PCR. STMN1 expression was significantly increased in malignant diffusely infiltrative astrocytomas compared with pilocytic astrocytoma (p < 0.0001). A strong correlation between MELK and STMN1 expressions was observed (r = 0.741, p < 0.0001) in glioblastoma (GBM) samples. However, no difference on survival times was found when compared GBM cases with upregulated and downregulated STMN1 (Breslow = 0.092, median survival time: 11 and 13 months, respectively). Functional assays knocking down MELK by siRNA in GBM cell line showed that gene and protein expression of both MELK and stathmin were diminished. On the other hand, when the same analysis was performed for STMN1, only stathmin gene and protein was silenced.
  
  
  CONCLUSIONS
  The results presented herein point stahtmin as a downstream target in the MELK pathway that plays a role in malignant progression of astrocytomas.
authors.affiliation: Laboratory of Molecular and Cellular Biology (LIM 15), Department of Neurology, School of Medicine, University of São Paul, Av. Dr Arnaldo 455, Cerqueira César, São Paulo, SP 01246-903 Brazil ; Center for Studies of Cellular and Molecular Therapy (NETCEM), University of Sao Paulo, São Paulo, Brazil.
authors.forename: Suely Kazue Nagahashi
authors.initials: SK
authors.lastname: Marie
authors.affiliation: Laboratory of Molecular and Cellular Biology (LIM 15), Department of Neurology, School of Medicine, University of São Paul, Av. Dr Arnaldo 455, Cerqueira César, São Paulo, SP 01246-903 Brazil.
authors.forename: Sueli Mieko
authors.initials: SM
authors.lastname: Oba-Shinjo
authors.affiliation: Laboratory of Molecular and Cellular Biology (LIM 15), Department of Neurology, School of Medicine, University of São Paul, Av. Dr Arnaldo 455, Cerqueira César, São Paulo, SP 01246-903 Brazil.
authors.forename: Roseli
authors.initials: R
authors.lastname: da Silva
authors.affiliation: Protein Chemistry Center and Department of Molecular and Cell Biology, Medical School of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900 Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: Gimenez
authors.affiliation: Laboratory of Molecular and Cellular Biology (LIM 15), Department of Neurology, School of Medicine, University of São Paul, Av. Dr Arnaldo 455, Cerqueira César, São Paulo, SP 01246-903 Brazil.
authors.forename: Gisele
authors.initials: G
authors.lastname: Nunes Reis
authors.affiliation: Cell Cycle Group, SFR Biosit, UMR 6290 CNRS Institut de Génétique et Développement de Rennes-Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, CS 34317, 35043 Rennes, Bretagne France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Tassan
authors.affiliation: Protein Chemistry Center and Department of Molecular and Cell Biology, Medical School of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900 Brazil.
authors.forename: Jose Cesar
authors.initials: JC
authors.lastname: Rosa
authors.affiliation: Center of Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo-ICESP, Av. Dr Arnaldo 251, 8th floor, Cerqueira César, São Paulo, SP 01246-000 Brazil.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Uno
keywords: Astrocytomas; MELK; Proteomics; Stathmin; qRT-PCR