title: SiRNA knockdown of the DEK nuclear protein mRNA enhances apoptosis and chemosensitivity of canine transitional cell carcinoma cells.
abstract: Transitional cell carcinoma (TCC) in dogs is an aggressive malignant neoplasm, originating in the epithelium of the urinary bladder. The DEK nuclear protein is overexpressed in several types of human bladder cancer, where it is involved in chromatin reconstruction, gene transcription and apoptosis. Since DEK represents a potential therapeutic target for canine TCC, this study was designed to investigate DEK expression in canine TCC and to determine the effects of DEK mRNA silencing on TCC cells in vitro. The gene expression profiles of seven selected cancer-associated genes was assessed in four canine TCC cell lines and expression of DEK protein was evaluated in bladder tissue biopsies from healthy dogs and those affected with cystitis or TCC. After transfection of four canine TCC cell lines with DEK-specific or scrambled siRNA, annexin V staining was performed to evaluate apoptosis, and methylthiazole tetrazolium assays were performed to assess both cell viability and sensitivity to carboplatin. DEK mRNA expression was relatively high in canine TCC cells and expression of the DEK protein was significantly greater in TCC tumours compared with the other tissue samples. After transfection with DEK-specific siRNA, apoptosis, cell growth inhibition, and enhanced sensitivity to carboplatin were observed in all TCC cells assessed. These research findings suggest that DEK could be a potential therapeutic target for canine TCC.
authors.affiliation: Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, N18 W9, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamazaki
authors.affiliation: Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, N18 W9, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Iwano
authors.affiliation: Laboratory of Anatomy, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, N18 W9, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Otsuka
authors.affiliation: North Lab, Shiroishi-ku, Hondori2, Kita8-35, Sapporo, Hokkaido 003-0027, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kagawa
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, N18 W9, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hoshino
authors.affiliation: Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, N18 W9, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hosoya
authors.affiliation: Laboratory of Veterinary Surgery, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, N18 W9, Sapporo, Hokkaido 060-0818, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okumura
authors.affiliation: Veterinary Teaching Hospital, Graduate School of Veterinary Medicine, Hokkaido University, Kita-ku, N18 W9, Sapporo, Hokkaido 060-0818, Japan. Electronic address: staka@vetmed.hokudai.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takagi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D055785:Gene Knockdown Techniques; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D015513:Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: DEK nuclear protein; Dog; SiRNA; Transitional cell carcinoma