| Grant number: | 14/18061-9 |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| Start date: | March 01, 2015 |
| End date: | August 31, 2017 |
| Field of knowledge: | Biological Sciences - Biochemistry - Chemistry of Macromolecules |
| Principal Investigator: | Sandra Martha Gomes Dias |
| Grantee: | Larissa Menezes dos Reis |
| Host Institution: | Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil |
Abstract The triple-negative breast cancer disease is characterized by the absence of progesterone and estrogen hormone receptors and HER2 membrane receptor, therefore is unresponsive to conventional treatments of disease. Among others, changes in the cellular metabolism are the molecular basis for the emergence and progression of the triple-negative phenotype, indicating that these alterations can provide good therapeutic targets. Increasing in glutamine consumption is one of the main metabolic alterations in tumor cells, being important for the anaplerosis of the Tricarboxylic Acid Cycle (TCA), since it replaces intermediates of this cycle used on biosynthetics routes. Studies conducted during the Masters program of this project's proponent showed that the glutamine dependence varied within 7 triple-negative breast cancer cel lines tested. qPCR assays of these cells grown with or without glutamine or in comparison to the more dependent cell line MDA-MB 231 showed increased expression of genes mainly related to the pathways of glycolysis/gluconeogenesis and fatty acid metabolism (beta-oxidation). These findings suggests the involvement of these pathways on compensating the lack of glutamine (or the lower need of such nutrient) to maintain the TCA cycle. This project aims at the study of these pathways in the cell lines MDA-MB-157, MDA-MB-468 and BT549, less dependent on the glutamine for growth. As a strategy, these cell lines will be subjected to the knock down of the above mentioned genes and evaluate the impact of this blockage associated to the absence of glutamine for proliferation assays, apoptosis, colony formation and migration/ invasion. To gain a better understanding on the nutrients responsible for balancing the absence of glutamine and the cellular processes in which those are involved, we will also perform gas chromatography-mass spectrometry (GC-MS) assays, using labeled isotopes nutrients (13C and 15N). (AU) | |
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