title: Gene therapy with SOCS1 for gastric cancer induces G2/M arrest and has an antitumour effect on peritoneal carcinomatosis.
abstract: BACKGROUND
  Suppressor of cytokine signaling1 (SOCS1) is a negative regulator of various cytokines. Recently, it was investigated as a therapeutic target in various cancers. However, the observed antitumour effects of SOCS1 cannot not be fully explained without taking inhibition of proliferation signalling into account. Our aim was to discover a new mechanism of antitumour effects of SOCS1 for gastric cancer (GC).
  
  
  METHODS
  We analysed the mechanism of antitumour effect of SOCS1 in vitro. In addition, we evaluated antitumour effect for GC using a xenograft peritoneal carcinomatosis mouse model in preclinical setting.
  
  
  RESULTS
  We confirmed that SOCS1 suppressed proliferation in four out of five GC cell lines. SOCS1 appeared to block proliferation by a new mechanism that involves cell cycle regulation at the G2/M checkpoint. We showed that SOCS1 influenced cell cycle-associated molecules through its interaction with ataxia telangiectasia and Rad3-related protein. The significant difference in therapeutic effects was noted in terms of the post-treatment weight and total photon count of the intra-abdominal tumours.
  
  
  CONCLUSIONS
  Forced expression of SOCS1 revealed a heretofore-unknown mechanism for regulating the cell cycle and may represent a novel therapeutic approach for the treatment of peritoneal carcinomatosis of GC.
authors.affiliation: 1] Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan [2] Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki city, Osaka, 567-0085, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Natatsuka
authors.affiliation: 1] Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan [2] Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki city, Osaka, 567-0085, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki city, Osaka, 567-0085, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.affiliation: Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki city, Osaka, 567-0085, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki city, Osaka, 567-0085, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ookawara
authors.affiliation: Department of Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa city, Chiba, 277-8577, Japan.
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
authors.affiliation: 1] Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan [2] Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki city, Osaka, 567-0085, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hara
authors.affiliation: 1] Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan [2] Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki city, Osaka, 567-0085, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nishigaki
authors.affiliation: Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki city, Osaka, 567-0085, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Harada
authors.affiliation: Department of Pharmacy, Takasaki University of Health and Welfare, 37-1 Nakaorui-machi, Takasaki city, Gunma 370-0033, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Makino
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kurokawa
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yamasaki
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan.
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Nakajima
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Takiguchi
authors.affiliation: Laboratory of Immune Regulation, Immunologu Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita city, Osaka, 565-0871, Japan.
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, 2-2 E2, Yamadaoka, Suita city, Osaka, 565-0871, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7-6-8 Saito-Asagi, Ibaraki city, Osaka, 567-0085, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D008822:Mice, Transgenic; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins