Wnt-5a gene expression in malignant human neuroblasts
Section snippets
The Wnt gene family
Subject of considerable investigation for more than 20 years, the Wnt gene family constitutes one of the major families of developmentally significant molecules, controlling a variety of processes such as cell fate specification, cell migration and cell polarity [1]. Wnt genes encode signaling proteins which are 38–45 kDa secreted cysteine-rich proteins with features typical of secreted growth factors. Nineteen different Wnt genes have been identified in the mouse and human genome (//www.stanford.edu/~rnusse/wntwindow.html
Low Wnt-5a expression in high-risk neuroblastoma
In order to identify metastatic-related genes in NB, we have performed a cDNA macroarray analysis of malignant neuroblasts derived from a human NB experimental model (IGR-N-91 model), established from an HR-NB and previously characterized in our laboratory [28]. Briefly, an in vitro neuroblastoma cell line, IGR-N-91, when injected subcutaneously in nude mice, yielded a primary tumor xenograft (PTX), and metastatic neuroblasts in two sites, myocardium (Myoc) and bone marrow (BM). Then PTX, Myoc
Induction of Wnt-5a expression in RA-differentiated malignant neuroblasts
The development of the neural crest and sympathetic nervous system depends on various factors such as FGFs and retinoic acid (RA) signals [33]. During embryogenesis, RA induces neuroectodermal differentiation with the formation of several cell types, including neurons, glia, and fibroblast-like cells. Interestingly, in undifferentiated human embryonal carcinoma, which do not express Wnt genes, Wnt expression has been shown to occur upon RA-induced differentiation [34], and more specifically to
Conclusions
The Wnt signaling cascade plays a decisive role in development and aberrant regulation is linked to cancer. Here, we described that Wnt-5a, an important regulator of morphogenetic movements during embryonal development [39] and recently involved in the proliferation of progenitor cells [40], is decreased in high-risk NB. These patients present a dramatic prognosis despite intensive high-dose and myeloablative chemotherapy, then followed by a maintenance regimen of 13-cis-retinoic acid [41], [42]
Acknowledgements
This work was supported by the Ligue Contre le Cancer, Comité de Montbéliard. Edited by Englishbooster S.A.
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2009, Biochemical and Biophysical Research CommunicationsCitation Excerpt :WNT5a is a WNT signal molecule involved in different WNT signaling pathways [30,31]. Low expression of WNT5a is found in high-risk neuroblastomas and thyroid carcinomas [32,33]. We have observed in this study that the down-regulation of WNT5a by amino acid limitation is correlated with a subsequent decrease in β-catenin accumulation in the nucleus.