title: Expression profile of Wilms Tumor 1 (WT1) isoforms in undifferentiated and all-trans retinoic acid differentiated neuroblastoma cells.
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.
authors.affiliation: Sections of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Maugeri
authors.affiliation: Sections of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy; San Raffaele Telematic University of Rome, Rome, Italy.
authors.forename: Agata Grazia
authors.initials: AG
authors.lastname: D'Amico
authors.affiliation: Sections of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Daniela Maria
authors.initials: DM
authors.lastname: Rasà
authors.affiliation: Sections of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Reitano
authors.affiliation: Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Saccone
authors.affiliation: Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Federico
authors.affiliation: Section of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Parenti
authors.affiliation: 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, Catania, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Magro
authors.affiliation: Sections of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Velia
authors.initials: V
authors.lastname: D'Agata
keywords: PI3K/Akt and MAPK/ERK signalling pathway; WT1 isoforms; Wilm's tumor 1 gene; alternative splice variants; neuroblastoma; tumor suppressor gene