Analysis of global gene expression regulated by the PRAME/EZH2 complex as a tool to discover new therapeutic targets against Cancer

• Grant number: 12/25380-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2013
• End date: October 31, 2015
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: João Gustavo Pessini Amarante Mendes
• Grantee: Sandy Adjemian Portela Catani
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The search for new treatments, more specific and less toxic, to fight cancer has been intensified over the past years. Part of the research in the biomedical area has been focused on studies of alterations involving genes regulating apoptosis resistance, proliferation, angiogenesis, metastasis, metabolism and inflammation, or genes conferring mechanism of escape against the immune response. Based on one of the processes responsible for conferring advantages of survival or growth of melanoma cells, our research group recently identified a new regulatory mechanism of TRAIL expression, involving the combined action of the proteins PRAME and EZH2, in chronic myeloid leukemia (CML). TRAIL is one of the most important weapon against cancer that our organism produces. This protein is responsible for initiating the extrinsic pathway of apoptosis, preferentially in tumor cells. In this sense, one of the mechanism of tumor escape from apoptosis by the immune system, is based on the reduced or lost expression of TRAIL, or in the resistance of its biological action. Therefore, our results suggest that the combined action of PRAME and EZH2 in CML (and possibly in other forms of cancer) provide epigenetic alterations able to promote malignancy to tumor cells. Based on this hypothesis, the objective of this work is to analyze the differential gene expression (micro-arrays) in cell lines established from patients with CML, modified by empty retroviral vectors, or containing shRNA sequences targeting PRAME or EZH2. This approach should reveal the genes that are regulated by the complex PRAME/EZH2. We believe that from the analysis of our results, using bioinformatics, we will be able to increase our knowledge on biochemical pathways activated or repressed during tumorigenesis and potentially reveal new therapeutic targets in CML, that could be used for other forms of cancer.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PORTELA CATANI, JOAO PAULO; MEDRANO, RUAN F. V.; HUNGER, ALINE; DEL VALLE, PAULO; ADJEMIAN, SANDY; ZANATTA, DANIELA BERTOLINI; KROEMER, GUIDO; COSTANZI-STRAUSS, EUGENIA; STRAUSS, BRYAN E.. Intratumoral Immunization by p19Arf and Interferon-beta Gene Transfer in a Heterotopic Mouse Model of Lung Carcinoma. TRANSLATIONAL ONCOLOGY, v. 9, n. 6, p. 565-574, DEC 2016. (11/10656-5, 12/25380-8, 13/09474-5, 14/11524-3, 13/25167-5)

PORTELA CATANI, JOAO PAULO; RIECHELMANN, RACHEL P.; ADJEMIAN, SANDY; STRAUSS, BRYAN E.. Near future of tumor immunology: Anticipating resistance mechanisms to immunotherapies, a big challenge for clinical trials. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 13, n. 5, p. 3-pg., 2017-01-01. (14/11524-3, 12/25380-8, 13/25167-5)