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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Proteomic analysis of low- to high-grade astrocytomas reveals an alteration of the expression level of raf kinase inhibitor protein and nucleophosmin

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Autor(es):
Gimenez, Marcela [1, 2] ; de Oliveira Souza, Vanessa Cristina [1, 2] ; Izumi, Clarice [1] ; Barbieri, Manuela R. [1, 2] ; Chammas, Roger [2, 3] ; Oba-Shinjo, Sueli Mieko [4] ; Uno, Miyuki [4] ; Nagahashi Marie, Suely Kazue [4] ; Rosa, Jose Cesar [1, 2]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Mol & Cell Biol, Sao Paulo - Brazil
[2] Fundacao Hemoctr Ribeirao Preto, CEPID CTC Ctr Cell Therapy, Ribeirao Preto - Brazil
[3] Lab Expt Oncol LIM 24, Dept Radiol, Sao Paulo - Brazil
[4] Univ Sao Paulo, Sch Med Sao Paulo, Dept Neurol, Mol & Cellular Biol Lab, Sao Paulo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: PROTEOMICS; v. 10, n. 15, p. 2812-2821, JUL 2010.
Citações Web of Science: 27
Resumo

Proteomic approaches have been useful for the identification of aberrantly expressed proteins in complex diseases such as cancer. These proteins are not only potential disease biomarkers, but also targets for therapy. The aim of this study was to identify differentially expressed proteins in diffuse astrocytoma grade II, anaplastic astrocytoma grade III and glioblastoma multiforme grade IV in human tumor samples and in non-neoplastic brain tissue as control using 2-DE and MS. Tumor and control brain tissue dissection was guided by histological hematoxylin/eosin tissue sections to provide more than 90% of tumor cells and astrocytes. Six proteins were detected as up-regulated in higher grade astrocytomas and the most important finding was nucleophosmin (NPM) (p < 0.05), whereas four proteins were down-regulated, among them raf kinase inhibitor protein (RKIP) (p < 0.05). We report here for the first time the alteration of NPM and RKIP expression in brain cancer. Our focus on these proteins was due to the fact that they are involved in the PI3K/AKT/mTOR and RAS/RAF/MAPK pathways, known for their contribution to the development and progression of gliomas. The proteomic data for NPM and RKIP were confirmed by Western blot, quantitative real-time PCR and immunohistochemistry. Due to the participation of NPM and RKIP in uncontrolled proliferation and evasion of apoptosis, these proteins are likely targets for drug development. (AU)

Processo FAPESP: 08/51360-9 - Proteomica funcional: estudo do papel da nucleofosmina na gliomagenese
Beneficiário:Marcela Gimenez
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 04/12133-6 - Procura de marcadores moleculares relacionados ao diagnóstico e prognóstico de tumores do sistema nervoso central
Beneficiário:Suely Kazue Nagahashi Marie
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 05/53039-5 - Abordagem proteomica na progressao tumoral de gliomas.
Beneficiário:Marcela Gimenez
Linha de fomento: Bolsas no Brasil - Mestrado