title: Partial sensitization of human bladder cancer cells to a gene-therapeutic             adenovirus carrying REIC/Dkk-3 by downregulation of BRPK/PINK1.
abstract: REIC/Dkk-3 is a tumor suppressor gene that was first identified as a gene             downregulated in association with immortalization of normal human fibroblasts.             We have demonstrated that an adenovirus carrying REIC/Dkk-3 (Ad-REIC) showed a             tumor-specific killing effect on a wide range of cancers. However, some human             cancers, bladder cancers in particular, are resistant to Ad-REIC. In this study,             we investigated the combination effect of downregulation of BRPK/PINK1 (PINK1)             and Ad-REIC on bladder cancer cells. Five bladder cancer cell lines among six             cell lines examined were resistant to Ad-REIC. Among the cell lines, the resistance             of two cell lines was probably due to low infection efficiency of the adenovirus.             PINK1-specific siRNA remarkably downregulated Bcl-xL and TRAP1 proteins and upregulated             BAX protein expression. Finally, downregulation of PINK1 partially sensitized             the other three cell lines that were resistant to Ad-REIC. This sensitization             was associated with increasing production of reactive oxygen species (ROS). These             results indicate that PINK1 is one of the key molecules for the mitochondrial             protection system and that PINK1 can be a new target molecule to sensitize bladder             cancer cells that are resistant to Ad-REIC.
authors.affiliation: Department of Cell Biology, Okayama University Graduate School                     of Medicine, Dentistry and Pharmaceutical Sciences, Kita-ku, Okayama 700-8558,                     Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Murata
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Ken
authors.initials: K
authors.lastname: Kataoka
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Huh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D018925:Chemokines; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy / Q000379:methods; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D051020:bcl-X Protein / Q000235:genetics; D000099202:PTEN-Induced Putative Kinase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; D018841:HSP90 Heat-Shock Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011494:Protein Kinases; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051020:bcl-X Protein; D000099202:PTEN-Induced Putative Kinase; C494811:BCL2L1 protein, human; C498624:DKK3 protein, human; C092306:TRAP1 protein, human