Expression profile of Wilms Tumor 1 (WT1) isoforms in undifferentiated and all-trans retinoic acid differentiated neuroblastoma cells
Grazia Maugeri1, Agata Grazia D’Amico1,2, Daniela Maria Rasà1, Rita Reitano1, Salvatore Saccone3, Concetta Federico3 , Rosalba Parenti4, Gaetano Magro5and Velia D’Agata1
1 Sections of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Italy
2 San Raffaele Telematic University of Rome, Italy
3 Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Italy
4 Section of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Italy
5 Section of Anatomic Pathology, Department of Medical and Surgical Sciences and Advanced Technologies, G.F. Ingrassia, Azienda Ospedaliero-Universitaria “Policlinico-Vittorio Emanuele”, University of Catania, Italy
Correspondence:
Velia D’Agata, email:
Keywords: Wilm’s tumor 1 gene, tumor suppressor gene, alternative splice variants, WT1 isoforms, neuroblastoma, PI3K/Akt and MAPK/ERK signalling pathway
Received: September 07, 2015 Accepted: January 29, 2016 Published: February 12, 2016
Abstract
Wilms tumor 1 gene (WT1) is a tumor suppressor gene originally identified in nephroblastoma. It is also expressed in neuroblastoma which represents the most aggressive extracranial pediatric tumor. Many evidences have shown that neuroblastoma may undergo maturation, by transforming itself in a more differentiated tumors such as ganglioneuroblastoma and ganglioneuroma, or progressing into a highly aggressive metastatic malignancy. To date, 13 WT1 mRNA alternative splice variants have been identified. However, most of the studies have focused their attention only on isoform of ~49 kDa. In the present study, it has been investigated the expression pattern of WT1 isoforms in an in vitro model of neuroblastoma consisting in undifferentiated or all-trans retinoic acid (RA) differentiated cells. These latter representing the less malignant phenotype of this tumor. Results have demonstrated that WT1.1-WT1.5, WT1.6-WT1.9, WT1.10 WT1.11-WT1.12 and WT1.13 isoforms are expressed in both groups of cells, but their levels are significantly increased after RA treatment. These data have also been confirmed by immunofluorescence analysis. Moreover, the inhibition of PI3K/Akt and MAPK/ERK, that represent two signalling pathway specifically involved in NB differentiation, induces an overexpression of WT1 isoforms. These data suggest that WT1 isoforms might be involved in differentiation of neuroblastic into mature ganglion cells.
