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Type: Artigo de periódico
Title: The Wnt signaling pathway regulates Nalm-16 b-cell precursor acute lymphoblastic leukemic cell line survival and etoposide resistance
Author: Thiago, LS
Costa, ES
Lopes, DV
Otazu, IB
Nowill, AE
Mendes, FA
Portilho, DM
Abreu, JG
Mermelstein, CS
Orfao, A
Rossi, MID
Borojevic, R
Abstract: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common malignancy in children. The Wnt signaling pathway has been found to be extensively involved in cancer onset and progression but its role in BCP-ALL remains controversial. We evaluate the role of the Wnt pathway in maintenance of BCP-ALL cells and resistance to chemotherapy. Gene expression profile revealed that BCP-ALL cells are potentially sensitive to modulation of Writ pathway. Nalm-16 and Nalm-6 cell lines displayed low levels of canonical activation, as reflected by the virtually complete absence of total beta-catenin in Nalm-6 and the beta-catenin cell membrane distribution in Nalm-16 cell line. Canonical activation with Wnt3a induced nuclear beta-catenin translocation and led to BCP-ALL cell death. Lithium chloride (LiCl) also induced a cytotoxic effect on leukemic cells. In contrast, both Wnt5a and Dkk-1 increased Nalm-16 cell survival. Also, Wnt3a enhanced the in vitro sensitivity of Nalm-16 to etoposide (VP-16) while treatment with canonical antagonists protected leukemic cells from chemotherapy-induced cell death. Overall, our results suggest that canonical activation of the Wnt pathway may exerts a tumor suppressive effect. thus its inhibition may support BCP-ALL cell survival. (C) 2009 Elsevier Masson SAS. All rights reserved.
Subject: B-Cell precursor acute lymphoblastic leukemia
Wnt signaling pathway
Drug resistance
Country: França
Editor: Elsevier France-editions Scientifiques Medicales Elsevier
Rights: fechado
Identifier DOI: 10.1016/j.biopha.2009.09.005
Date Issue: 2010
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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