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Investigation of ATM (Ataxia Telangiectasia Mutated) kinase function in the resistance of glioblastoma multiforme cells to ionizing radiation

Grant number: 12/16877-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2012
Effective date (End): July 31, 2015
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Valeria Valente
Grantee:Renato Petitto Netto
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Glioblastoma multiforme (GBM) brain tumor is the most common and deadly and usually leads the patient to death in approximately 14 months after diagnosis. The treatment consists of surgical removal of tumor followed by radiotherapy and chemotherapy. However, due to the high resistance of tumor cells, the tumor grows again few weeks after surgery. The ATM is a protein kinase that may be involved with resistance to radiotherapy GBM cells, is needed to generate intracellular signals produced in response to various types of lesions in DNA. A recently detected molecular alteration in glioblastomas is the overexpression of the protein HJURP (Holliday Junction Recognizing Protein). HJURP, a protein that is highly overexpressed in different tumor types, is related to the repair of double-stranded breaks in DNA by homologous recombination and is regulated by means of ATM cells, osteosarcoma. Previous data from our laboratory demonstrating that there are variations in the levels of expression of HJURP different glioma cell lines and show an association between levels of expression and greater HJURP resistance of cells to ionizing radiation. In this project we intend to investigate the correlation between the expression levels of ATM and the resistance of GBM cells to ionizing radiation. In addition, we also intend to check for correlation between the expression levels of ATM and HJURP, which will be obtained in another laboratory project.

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