title: Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene.
abstract: A number of chromosomal abnormalities including 19q deletions have been associated with the formation of human gliomas. In this study, we employed a proteomics-based approach to identify possible genes involved in glioma tumorigenesis which may serve as potential diagnostic molecular markers for this type of cancer. By comparing protein spots from gliomas and non-tumor tissues using two-dimensional (2D) gel electrophoresis, we identified 11 up-regulated proteins and four down-regulated proteins in gliomas. Interestingly, we also discovered that a group of cytoskeleton-related proteins are differentially regulated in gliomas, suggesting the involvement of cytoskeleton modulation in glioma pathogenesis. We then focused on the cytoskeleton-related protein, SIRT2 (sirtuin homologue 2) tubulin deacetylase, which was down-regulated in gliomas. SIRT2 is located at 19q13.2, a region known to be frequently deleted in human gliomas. Subsequent Northern blot analysis revealed that RNA expression of SIRT2 was dramatically diminished in 12 out of 17 gliomas and glioma cell lines, in agreement with proteomic data. Furthermore, ectopic expression of SIRT2 in glioma cell lines led to the perturbation of the microtubule network and caused a remarkable reduction in the number of stable clones expressing SIRT2 as compared to that of a control vector in colony formation assays. These results suggest that SIRT2 may act as a tumor suppressor gene in human gliomas possibly through the regulation of microtubule network and may serve as a novel molecular marker for gliomas. Additional proteins were also identified, whose function in gliomas was previously unsuspected.
authors.affiliation: Department of Molecular and Cell Genetics, Graduate School of Medical Science, Tottori University, Nishimachi 86, Yonago, Tottori 683-8503, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Hiratsuka
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Inoue
authors.forename: Tosifusa
authors.initials: T
authors.lastname: Toda
authors.forename: Narimichi
authors.initials: N
authors.lastname: Kimura
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shirayoshi
authors.forename: Hideki
authors.initials: H
authors.lastname: Kamitani
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Eisaku
authors.initials: E
authors.lastname: Ohama
authors.forename: Candice G T
authors.initials: CG
authors.lastname: Tahimic
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kurimasa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Oshimura
mesh_terms: D015152:Blotting, Northern; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D002455:Cell Division; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D004794:Enzyme Repression; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D006801:Humans; D008870:Microtubules / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000032:analysis; D040901:Proteomics; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D009363:Neoplasm Proteins; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D037761:Sirtuins