Modulation of kinases and microRNAs by protein tyrosine phosphatase and mechanism of resistance of leukemic cells

• Grant number: 11/15143-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): April 01, 2012
• Effective date (End): March 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Carmen Veríssima Ferreira
• Grantee: Thaís Franchini Tornatore de Araujo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The progress of knowledge about the molecular basis of cancer, has reinforced the concept of this multifactorial disease. The challenge in the coming years is to develop strategies to understand the molecular framework of tumor cells, therapeutic approaches to establish "smart" and personalized therapy in order to increase efficiency, specificity and quality of life of patients. In this context, the processes responsible for acquisition of resistance to chemotherapeutic agents is an important area of research. This project aims to determine the general mechanism by which the low molecular weight protein tyrosine phosphatase (LMWPTP) contributes to resistance of leukemic cells by focusing on the modulation of kinases and transcription of microRNAs. The following points underlying the proposal: 1) it was observed that the inhibition or gene silencing of LMWPTP increases sensitivity of leukemic cells to chemotherapy, 2) quinomic profile of resistant leukemic cells to mitoxantrone revealed 34 most active kinases, such as activators of progression cell cycle, receptor tyrosine kinase and MAPKs, 3) LMWPTP silenced on resistant leukemia cells (Lucena) caused a decrease of the microRNA Let7a expression. Therefore, the proposal is innovative and multidisciplinary, and can give great contribution to basic and applied research in the field of cancer study. The experimental strategies also make the project highly competitive in terms of global research.