title: Wilms' tumor gene 1 silencing inhibits proliferation of human osteosarcoma MG-63 cell line by cell cycle arrest and apoptosis activation.
abstract: Wilms' tumor gene 1 (WT1) plays complex roles in tumorigenesis, acting as tumor suppressor gene or an oncogene depending on the cellular context. A high WT1 expression level was described in various types of human bone and soft-tissue sarcomas, including osteosarcoma (OS), but its function in carcinogenesis is not yet well understood. This study investigated WT1 both in human OS tissues and in human OS MG-63 cell line in which WT1 gene is up-regulated. The results demonstrated that WT1 is expressed in 50% of human OS cases. WT1-silenced MG-63 cells showed deregulation of proteins of cell cycle and down-regulation of PI3K/AKT pathway. Induction of apoptotic programme was also established by activation of caspase-3 and increase of Bax/Bcl2 ratio and p53 protein. This study provided new findings on role of WT1 and indicated an association between WT1 expression, cell cycle and apoptotic machinery. In conclusion, WT1 acts as a tumour promoter in osteosarcoma and it could be a potential therapeutic target.
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 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: Rosanna
authors.initials: R
authors.lastname: Avola
authors.affiliation: Department of Biomedical and Biotechnological Sciences, Physiology Section, University of Catania, 95125 Catania, Italy.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Vicario
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: Department G.F. Ingrassia, Azienda Ospedaliero-Universitaria ''Policlinico-Vittorio Emanuele'' Anatomic Pathology, University of Catania, 95125 Catania, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Salvatorelli
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
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
mesh_terms: D000293:Adolescent; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D016162:Genes, Wilms Tumor / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology*; D059467:Transcriptome; D025721:WT1 Proteins / Q000096:biosynthesis* / Q000235:genetics; D055815:Young Adult
chemical_list: D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: WT1; apoptosis; cell cycle; oncogene; osteosarcoma