title: Wilms' tumor gene WT1 17AA(-)/KTS(-) isoform induces morphological changes and promotes cell migration and invasion in vitro.
abstract: The wild-type Wilms' tumor gene WT1 is overexpressed in human primary leukemia and in a wide variety of solid cancers. All of the four WT1 isoforms are expressed in primary cancers and each is considered to have a different function. However, the functions of each of the WT1 isoforms in cancer cells remain unclear. The present study demonstrated that constitutive expression of the WT1 17AA(-)/KTS(-) isoform induces morphological changes characterized by a small-sized cell shape in TYK-nu.CP-r (TYK) ovarian cancer cells. In the WT1 17AA(-)/KTS(-) isoform-transduced TYK cells, cell-substratum adhesion was suppressed, and cell migration and in vitro invasion were enhanced compared to that in mock vector-transduced TYK cells. Constitutive expression of the WT1 17AA(-)/KTS(-) isoform also induced morphological changes in five (one gastric, one esophageal, two breast and one fibrosarcoma) of eight cancer cell lines examined. No WT1 isoforms other than the WT1 17AA(-)/KTS(-) isoform induced the phenotypic changes. A decrease in alpha-actinin 1 and cofilin expression and an increase in gelsolin expression were observed in WT1 17AA(-)/KTS(-) isoform-transduced TYK cells. In contrast, co-expression of alpha-actinin 1 and cofilin or knockdown of gelsolin expression by small interfering RNA restored WT1 17AA(-)/KTS(-) isoform-transduced TYK cells to a phenotype that was comparable to that of the parent TYK cells. These results indicated that the WT1 17AA(-)/KTS(-) isoform exerted its oncogenic functions through modulation of cytoskeletal dynamics. The present results may provide a novel insight into the signaling pathway of the WT1 gene for its oncogenic functions.
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Tanyarat
authors.initials: T
authors.lastname: Jomgeow
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Naoko
authors.initials: N
authors.lastname: Tsuji
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Ken
authors.initials: K
authors.lastname: Ito
authors.forename: Asako
authors.initials: A
authors.lastname: Tsuda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Tatsumi
authors.forename: Nao
authors.initials: N
authors.lastname: Sakaguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takashima
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shirakata
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.forename: Naoki
authors.initials: N
authors.lastname: Hosen
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawakami
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Itoh
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000185:Actinin / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D048429:Cell Size; D018260:Gelsolin / Q000378:metabolism; D016162:Genes, Wilms Tumor / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D020033:Protein Isoforms; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins / Q000378:metabolism*
chemical_list: D018260:Gelsolin; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D025721:WT1 Proteins; D000185:Actinin