Study molecular and functional of oncoprotein SET

• Grant number: 06/06334-4
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: April 01, 2007
• End date: March 31, 2011
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Andréia Machado Leopoldino
• Grantee: Andréia Machado Leopoldino
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 09/10783-7 - Molecular study of hnRNP K and SET proteins on transcription and translational proteins associated in oral tumorigenesis, BP.PD; 07/02223-6 - Study of proteins selected as potencial markers in head and neck cancer, BP.MS

Abstract

The boarding of this project is that used during the post doc in the exterior in the National Institute of Health (NIH, U.S.A.) (FAPESP process: 05/03380-2) and it constitutes a new line of research to be implanted and to be established in the Faculty of Pharmaceutical Sciences of Ribeirão Preto, USP. The central objective is the protein study selected as markers tumoral using functional studies based mainly in interference RNA. Recently, we validate in samples of tumor of head and neck, a new tumoral marker, protein SET (results gotten during the PD in the exterior), the screening had been also identified for the group of the Dr. Silvio Gutkind during one study using microarrangements of RNA in oral tumors. In present the proposal, continuity will be given to the study of this tumoral marker to increase the knowledge on its function and to verify its therapeutically potential as target. Important results had been gotten in this first evaluation of the SET that had shown its participation in one of the ways most important for tumorgenesis, way PTEN/AKT (article in preparation). The analysis using tissue array showed that this protein presents over expression in about 80% of the tumors, what confers to this protein a oncogene role. It is intended to also study other proteins already selected in the PD in Brazil (FAPESP process: 02/09388-7) and to contribute with the study of the study of the new markers that will be identified to the long one of Clinical Genome of the Cancer (FAPESP, process: 02/01520-3). During the PD in the exterior diverse methodologies of study had been used (RNA of interference, shorts hairpin RNA, super protein expression in cellular ancestries, western blotting, analysis FACS, tissue arrays) to study the participation of protein SET in tumorgenesis of head and neck. When we made the know down of this protein in cells tumorais HNSCC, the cells had died. This showed that the SET protein could be a therapeutically target potential or one to help in the existing therapies. However, for the application of this protein as therapeutically target, more functional studies will be necessary. Thus, I also consider in this project the continuity of the functional study of oncogene protein SET and the inquiry of the participation in tumorgenesis of other selected markers already. This project will have the participation of Dr. J. Silvio Gutkind (NIH) in the continuity of the functional studies of the SET, and will contribute with the Clinical Genome of the Cancer Project. After the accomplishment of the period of training in the exterior and the definition of the research area, I believe that the project presents focus and constitutes a new line of research to be established in the Faculty of Pharmaceutical Sciences of Ribeirão Preto, USP, aiming at to the functional study of tumoral markers using tools as RNA of interference and super expression of proteins in cellular human lines, to study ways of cellular signaling and the potential of the therapeutically markers as target. (AU)

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)

LEOPOLDINO, ANDREIA M.; SQUARIZE, CRISTIANE H.; GARCIA, CRISTIANA B.; ALMEIDA, LUCIANA O.; PESTANA, CEZAR R.; SOBRAL, LAYS M.; UYEMURA, SERGIO A.; TAJARA, ELOIZA H.; GUTKIND, J. SILVIO; CURTI, CARLOS. SET protein accumulates in HNSCC and contributes to cell survival: Antioxidant defense, Akt phosphorylation and AVOs acidification. Oral Oncology, v. 48, n. 11, p. 1106-1113, NOV 2012. (05/03380-2, 10/20384-0, 09/52228-0, 06/06334-4)

LEOPOLDINO, ANDREIA M.; SQUARIZE, CRISTIANE H.; GARCIA, CRISTIANA B.; ALMEIDA, LUCIANA O.; PESTANA, CEZAR R.; POLIZELLO, ANA C. M.; UYEMURA, SERGIO A.; TAJARA, ELOIZA H.; GUTKIND, J. SILVIO; CURTI, CARLOS. Accumulation of the SET protein in HEK293T cells and mild oxidative stress: cell survival or death signaling. Molecular and Cellular Biochemistry, v. 363, n. 1-2, p. 65-74, APR 2012. (05/03380-2, 09/52228-0, 06/06334-4)