1. A resistência das células T98G e U87MG à temozolamida está correlacionada com a expressão de genes de reparo de DNA.
- Author
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Ferreira de Sousa, Juliana, Di Cristofaro, Luis Fernando, Bortolozo Serafim, Rodolfo, Petitto Netto, Renato, de Oliveira Souza, Felipe, Pienna Soares, Christiane, and Valente, Valeria
- Abstract
Gliomas are brain tumors pathologically defined by the presence of cells with histological and immunohistochemical characteristics of glial differentiation. Among them, astrocytomas are the most common in adults. These tumors usually show diffuse infiltration into adjacent tissue, are resistant to treatment and have a natural tendency to malignant progression. The current standard treatment consists in surgical removal of the tumor followed by radiotherapy and concurrent chemotherapy. However, the prognosis remains extremely poor. The first line chemotherapy for GBM treatment is the DNA alkylating agent temozolamide (TMZ). Nevertheless, TMZ-induced damage can be reversed by the action of DNA repair machinery that prevents cell death and leads to relapse. In this study we correlated the expression of the DNA damage-signaling gene, ATM kinase, and the DNA repair genes BRCA2, BRIP1, EXO1, NEIL3, RAD54L and XRCC2, with the resistance of T98G and U87MG cell lines to TMZ. T98G cells were more resistant to TMZ treatment and showed overexpression of all DNA repair genes, while ATM kinase was down regulated. We also observed that U87MG cells, more sensitive to TMZ, have reduced expression of ATM, BRCA2 and EXO1. Therefore, these data suggest a positive correlation between the expression of DNA repair genes and the resistance of GBM cells to TMZ. [ABSTRACT FROM AUTHOR]
- Published
- 2015