Ionizing radiation-induced gene expression changes in TP53 proficient and deficient glioblastoma cell lines

Autor(es)

Godoy, P. R. D. V. ; Mello, S. S. ; Magalhaes, D. A. R. ; Donaires, F. S. ; Nicolucci, P. ; Donadi, E. A. ; Passos, G. A. ; Sakamoto-Hojo, E. T.

• Tipo de documento: Artigo Científico
• Fonte: MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS; v. 756, n. 1-2, p. 10-pg., 2013-08-30.

Resumo

The genetic heterogeneity presented by different cell lines derived from glioblastoma (GBM) seems to influence their responses to antitumoral agents. Although GBM tumors present several genomic alterations, it has been assumed that TP53, frequently mutated in GBM, may to some extent be responsible for differences in cellular responses to antitumor agents, but this is not clear yet. To directly determine the impact of TP53 on GBM response to ionizing radiation, we compared the transcription profiles of four GBM cell lines (two with wild-type (WT) TP53 and two with mutant (MT) TP53) after 8 Gy of gamma-rays. Transcript profiles of cells analyzed 30 min and 6 h after irradiation showed that WT TP53 cells presented a higher number of modulated genes than MT TP53 cells. Our findings also indicate that there are several pathways (apoptosis, DNA repair/stress response, cytoskeleton organization and macromolecule metabolic process) in radiation responses of GBM cell lines that were modulated only in WT TP53 cells (30 min and 6 h). Interestingly, the majority of differentially expressed genes did not present the TP53 binding site, suggesting secondary effects of TP53 on transcription. We conclude that radiation-induced changes in transcription profiles of irradiated GBM cell lines mainly depend on the functional status of TP53. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 06/01953-8 - Coordenacao entre as respostas celulares ao estresse genotoxico causado pela radiacao ionizante em linhagens de glioma proficientes e mutantes para o gene tp53.
• Beneficiário: Paulo Roberto D'Auria Vieira de Godoy
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 04/15611-6 - Mecanismos envolvidos nas respostas celulares aos compostos antitumorais e raios-gama em diferentes tipos de celulas humanas.
• Beneficiário: Elza Tiemi Sakamoto Hojo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 06/01947-8 - Sinalização celular e molecular em resposta ao estresse genotóxico e/ou geração de dano oxidativo em linhagens de glioma, linfócitos de pacientes com diabetes e Mal de Alzheimer
• Beneficiário: Elza Tiemi Sakamoto Hojo
• Modalidade de apoio: Auxílio à Pesquisa - Regular