title: Suppressor of cytokine signalling-1 induces significant preclinical antitumor effect in malignant melanoma cells.
abstract: Malignant melanoma is the most aggressive form of skin cancer, responsible for the majority of skin cancer-related deaths. Metastatic melanoma is resistant to surgery, radiation or chemotherapy, and an effective therapy has not yet been established. Our study investigated the therapeutic potential of the suppressor of cytokine signalling-1 (SOCS-1), an endogenous inhibitor of the intracellular cytokine signalling pathway, for treating melanoma. Adenovirus vectors encoding the SOCS-1 gene were used to overexpress SOCS-1 in three melanoma cell lines (G361, SK-MEL5 and SK-MEL28). In G361 and SK-MEL5, overexpression of SOCS-1 significantly reduced cell proliferation and induced apoptosis in vitro and in vivo. Furthermore, we indicated that the antiproliferative effect of SOCS-1 correlated not only with decreased levels of the activation of signal transducer and activator of transcription (STAT)3 but also with increased levels of p53 expression and phosphorylation. These findings indicate the potential for clinical use of SOCS-1 for melanoma treatment.
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Japan.|Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Tagami-Nagata
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Serada
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanemura
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Japan.|Department of Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Nakatsuka
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Japan.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Ohkawara
authors.affiliation: Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murota
authors.affiliation: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan.
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
authors.affiliation: Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
authors.affiliation: Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Naka
mesh_terms: D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D015316:Genetic Therapy; D006801:Humans; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016159:Tumor Suppressor Protein p53
keywords: JAK/STAT; apoptosis; malignant melanoma; p53; suppressor of cytokine signalling-1