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Shotgun proteomics in studies of glioma, the interactions of protein complexes with nucleophosmin and proteome/phosphoproteome of glioblastoma multiforme (GBM) derived cell lines stimulated by EGF

Grant number: 11/07568-7
Support Opportunities:Regular Research Grants
Duration: February 01, 2012 - January 31, 2014
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:José César Rosa
Grantee:José César Rosa
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated researchers: Clarice Izumi ; Hélen Julie Laure ; Suely Kazue Nagahashi Marie


Gliomas are the most malignant of brain tumors, they are very heterogeneous, and have features like high cell proliferation, hyperplasia, necrotic areas and extensive formation of new blood vessels. Among them, astrocytomas correspond to 60% of brain tumors and usually affect the adult population, the survival prognosis is poor, or up to 12-14 months of life, since they have a tendency to recurrence and malignant progression, not responding to treatment, generally including aggressive surgical resection, radiotherapy and chemotherapy. Our group recently reported the altered expression of proteins nucleophosmin and RKIP in glioblastoma multiforme (GBM), and these proteins are involved in two signaling pathways, PI3K/AKT/mTOR and RAS/ RAF / MAPK, known to be important for the formation of glioma and downstream of EGF receptor. In this proposal we intend to investigate using proteomics strategy: 1) tumors of astrocytomas and oligodendrogliomas, 2) proteome of cell lines derived from GBM and some proteins correlations with assays of proliferation, migration and apoptosis, 3) effect of EGF stimulation in phosphoproteome of cell lines derived from GBM, 4) characterization of multi-protein complex to target the central protein-protein interactions with nucleophosmin (NPM1). To achieve these goals we will use quantitative proteomics by labeling with isobaric iTRAQ and the incorporation of stable isotopes of amino acids (SILAC). By using iTRAQ proteomics strategy, we intend to study differentially expressed proteins in grade II astrocytomas (4 cases); GBM short survival <12 months (4 cases); GBM long survival> 16 months (4 cases), oligodendroglioma grade II (4 cases) and anaplastic oligodendroglioma (4 cases) compared to a pool of non-neoplasic brain tissue (9 patients). Using proteomic strategy with the incorporation of metabolic SILAC, we will investigate the changes of the proteome and phosphoproteome of U87MG and T98G cell lines under stimulation with EGF. Therefore, we hope to contribute to the generation of knowledge in cancer, progress in proteomics technology and consolidate our initial studies on tumor progression of glioma. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GIMENEZ, MARCELA; NAGAHASHI MARIE, SUELY KAZUE; OBA-SHINJO, SUELI; UNO, MIYUKI; IZUMI, CLARICE; OLIVEIRA, JOAO BOSCO; ROSA, JOSE CESAR. Quantitative proteomic analysis shows differentially expressed HSPB1 in glioblastoma as a discriminating short from long survival factor and NOVA1 as a differentiation factor between low-grade astrocytoma and oligodendroglioma. BMC CANCER, v. 15, . (04/12133-6, 13/02162-8, 13/06315-3, 11/07568-7)
GIMENEZ, MARCELA; MARIE, SUELY K. N.; OBA-SHINJO, SUELI M.; UNO, MIYUKI; DA SILVA, ROSELI; LAURE, HELEN JULIE; IZUMI, CLARICE; OTAKE, ANDREIA; CHAMMAS, ROGER; ROSA, JOSE CESAR. Quantitative proteomic analysis and functional studies reveal that nucleophosmin is involved in cell death in glioblastoma cell line transfected with siRNA. PROTEOMICS, v. 12, n. 17, SI, p. 2632-2640, . (04/12133-6, 11/07568-7)

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