Study of NRF2 and KEAP1 genes involved in antioxidative response in thyroid cancer

• Grant number: 12/00164-0
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2012
• End date: July 31, 2014
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Debora Lucia Seguro Danilovic
• Grantee: Debora Lucia Seguro Danilovic
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The oxidative stress is a dynamic condition characterized by the imbalance between oxidants and antioxidants. Firstly, reactive oxygen species (ROS), without the counteraction of antioxidants, promote DNA damage. However, antioxidants agents, such as NRF2 which activates cytoprotector genes, favor the survival of cancerigenous cells. Under basal conditions, the repressor protein KEAP1 binds to NRF2 in the cytoplasm and promotes its degradation. In the presence of ROS, KEAP1 is inactivated and releases NRF2 resulting in its nuclear translocation. The presence of mutations in the genes NRF2 e KEAP1, favoring increased expression of NRF2 and action, are described in association with several types of neoplasias. In vitro studies observed increased expression of NRF2 in anaplastic and poorly differentiated thyroid carcinoma cell lines and in primary murine cells with the expression of oncogenic alleles of K-Ras, B-Raf, usually associated with differentiated thyroid carcinomas. The aims of this study are to evaluate the presence of mutations in the genes NRF2 e KEAP1 in differentiated, poorly differentiated and anaplastic thyroid carcinomas; and to evaluate the expression of NRF2 in differentiated thyroid carcinomas. In mutational analysis, parafinated tumoral tissue samples of 120 patients with histological diagnosis of differentiated, poorly differentiated and anaplastic thyroid carcinomas will be evaluated. In the study of NRF2 expression, tumoral tissue samples conserved in liquid nitrogen of 10 patients with differentiated thyroid carcinoma will be analyzed. (AU)