The Wnt signaling pathway regulates Nalm-16 b-cell precursor acute lymphoblastic leukemic cell line survival and etoposide resistance - 04/01/10
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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 Wnt pathway. Nalm-16 and Nalm-6 cell lines displayed low levels of canonical activation, as reflected by the virtually complete absence of total β-catenin in Nalm-6 and the β-catenin cell membrane distribution in Nalm-16 cell line. Canonical activation with Wnt3a induced nuclear β-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.
Le texte complet de cet article est disponible en PDF.Keywords : B-Cell precursor acute lymphoblastic leukemia, Wnt signaling pathway, Drug resistance
Plan
Funded by BZG. |
Vol 64 - N° 1
P. 63-72 - janvier 2010 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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