Role Of mTOR and iNOS on colon tumor cell viability

• Grant number: 14/08523-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2014
• End date: June 30, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Hugo Pequeno Monteiro
• Grantee: Talita Yukimi Leite
• Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The regulation of cell proliferation and survival signaling pathways is critical for cellular homeostasis and abnormalities in this regulation are associated with the establishment of tumors. The TOR signaling pathway, conserved among species, regulates multiple processes in response to nutrient availability, including translation, transcription, cell proliferation and cell senescence. Mutations in genes coding proteins participating in this pathway and the activation of mTOR itself are associated with the development of tumors. Nitric oxide (NO*) is a lipid permeable layer free radical which works as a messenger in intracellular signaling and intercellular communication. In mammals, the enzyme nitric oxide synthase are mainly responsible for the biosynthesis of NO*. Three isoforms of NOS are known, neuronal NOS (nNOS/NOS1), endothelial NOS (eNOS/NOS3) and induced NOS (iNOS/NOS2) . The expression of these isoforms in different types of tumors has been often associated with malignancy.Recent studies have shown an association between the regulation of the mTOR signaling pathway and expression and stabilization of iNOS. Pervin et al (2007) shows that the use of exogenous NO* donor stimulates signaling processes mediated by mTOR. Other studies have shown an inverse relationship between the activation of mTOR and the establishment of the senescence phenotype. The relationship between the generation of NO* and their effects on cell and the mTOR signaling pathway, as on senescence and tumor development has not yet been elucidated. This project aimed to study how the induction and inhibition of mTOR signaling pathway is associated with production of NO*, senescence and colon tumor progression.