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Proteomic study of epithelial to mesenchymal transition in breast cancer

Grant number: 12/02518-4
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2012
Effective date (End): January 31, 2014
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Vitor Marcel Faça
Grantee:Daniele Albuquerque
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:11/09740-1 - Identification and validation of metastasis-related molecular signatures -In-Depth and targeted proteomic analysis of epithelial-mesenchymal transition in adenocarcinomas, AP.JP

Abstract

Breast cancer kills more than 450 thousand women worldwide every year. Because of that, this disease is considered one of the priorities in women public health. Despite recent scientific advances toward disease molecular characterization and imaging methods for breast cancer detection, several challenges related to the disease heterogeneity remain unsolved, turning the diagnostic and treatment often difficult. Breast cancer is usually caused by genetic or epigenetic alterations. Genetic mutations in BRCA-1 and BRCA-2 genes as well as in TP53, PTEN, ATM, CDH1, CHEK2 e STK11 (LKB1) are often detected. In addition to these known frequent mutations, growth factors such as TGB- ² and EGF play important roles in breast cancer progression and metastasis. Interestingly, TGB- ² and EGF are also inducers of the Epithelial to Mesenchymal Transition (EMT), in which epithelial cells lose their intracellular contacts and acquire migratory abilities. In fact, EMT is considered one of the mechanisms responsible for tumor progression and metastasis in adenocarcinomas as well as to the process of cancer stem cells generation. Here in our study, we will perform an in-depth qualitative and quantitative proteomic analysis based on stable isotope labeling in cell culture (SILAC) followed by cellular and protein fractionation in order to elucidate the alterations promoted by the induction of EMT in breast cancer cell lines. Breast cancer cells will be treated with TGB- ² and EGF in order to induce migratory and invasive characteristics achieved during EMT and that can be representative of a controlled metastatic process. With this approach we expect to identify proteins relevant to breast cancer progression and metastasis and that can be further evaluated as potential diagnostic or therapeutic targets for metastatic disease.