title: Wilms' tumor gene 1 (WT1) silencing inhibits proliferation of malignant peripheral nerve sheath tumor sNF96.2 cell line.
abstract: Wilms' tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumor suppressor gene or an oncogene depending on the cellular context. WT1 expression has been variably reported in both benign and malignant peripheral nerve sheath tumors (MPNSTs) by means of immunohistochemistry. The aim of the present study was to characterize its potential pathogenetic role in these relatively uncommon malignant tumors. Firstly, immunohistochemical analyses in MPNST sNF96.2 cell line showed strong WT1 staining in nuclear and perinuclear areas of neoplastic cells. Thus, we investigated the effects of silencing WT1 by RNA interference. Through Western Blot analysis and proliferation assay we found that WT1 knockdown leads to the reduction of cell growth in a time- and dose-dependent manner. siWT1 inhibited proliferation of sNF96.2 cell lines likely by influencing cell cycle progression through a decrease in the protein levels of cyclin D1 and inhibition of Akt phosphorylation compared to the control cells. These results indicate that WT1 knockdown attenuates the biological behavior of MPNST cells by decreasing Akt activity, demonstrating that WT1 is involved in the development and progression of MPNSTs. Thus, WT1 is suggested to serve as a potential therapeutic target for MPNSTs.
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Physiology Section, University of Catania, 95125 Catania, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Parenti
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Physiology Section, University of Catania, 95125 Catania, Italy.
authors.forename: Venera
authors.initials: V
authors.lastname: Cardile
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Physiology Section, University of Catania, 95125 Catania, Italy.
authors.forename: Adriana Carol Eleonora
authors.initials: AC
authors.lastname: Graziano
authors.affiliation: Department of Drug Sciences, Pharmacology and Toxicology Section, University of Catania, 95125 Catania, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Parenti
authors.affiliation: Business Unit Oncology, Nerviano Medical Sciences S.r.l., 20014 Nerviano Milano, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Venuti
authors.affiliation: Business Unit Oncology, Nerviano Medical Sciences S.r.l., 20014 Nerviano Milano, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Bertuccio
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Physiology Section, University of Catania, 95125 Catania, Italy.
authors.forename: Debora Lo
authors.initials: DL
authors.lastname: Furno
authors.affiliation: Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele" Anatomic Pathology, University of Catania, 95125 Catania, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Magro
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009442:Neurilemmoma / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D025721:WT1 Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D025721:WT1 Proteins; C583751:WT1 protein, human; D019938:Cyclin D1