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Investigation of the role of IRS1 in the beta-catenin signaling pathway in acute lymphoblastic leukemia

Grant number: 13/26213-0
Support type:Scholarships in Brazil - Master
Effective date (Start): May 01, 2014
Effective date (End): April 30, 2016
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Fabíola Traina
Grantee:Jaqueline Cristina Fernandes
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The acute lymphoblastic leukemia (ALL) is the most common cancer in childhood. The incidence of ALL is lower in adults, but, in this population, the disease is associated with a worse prognosis and a probability of long term survival less than 40%. ALL is a heterogeneous group of malignancies characterized by abnormal proliferation and accumulation of immature cells in the bone marrow, which impairs the production of erythrocytes, leukocytes and platelets. The insulin receptor substrate-1 (IRS1) is well known as a cytosolic protein involved in signal transduction, but also plays a role in malignant transformation, being highly expressed in many cancers. In ALL BCR -ABL positive, the IRS1 expression is associated with a poor prognosis. The IRS1, in certain circumstances, is translocated to the nucleus. In fibroblasts, nuclear IRS1 was found to interact with ²-catenin and to induce c-myc and cyclin D1 transcription. When highly expressed, c-myc and cyclin D1 may act as oncogenes, contributing to the development of cancers, including hematopoietic neoplasm. Our group of investigation has previous observed that IRS1 is located in the cytoplasm and nucleous of leukemia cells. However, the role of nuclear IRS1 in leukemia cells has not been investigated. Thus, this study aims to investigate the role of nuclear IRS1 in the ²-catenin pathway and in c-myc and cyclin D1 expression in LLA. Patients with diagnosis of ALL will be included in the study of gene expression (IRS1, ²-catenin, c-myc and cyclin D1). ALL cell lines will be used for the studies of protein expression and associations, and will be submitted to IRS1 silencing and functional studies.

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
FERNANDES, Jaqueline Cristina. Investigation of the role of IRS1 in the β-catenin signaling pathway in acute lymphoblastic leukemia. 2016. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto Ribeirão Preto.

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