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Suppressor of cytokine signalling‐1 induces significant preclinical antitumor effect in malignant melanoma cells
Authors:Naoko Tagami‐Nagata  Satoshi Serada  Minoru Fujimoto  Atsushi Tanemura  Rie Nakatsuka  Tomoharu Ohkawara  Hiroyuki Murota  Tadamitsu Kishimoto  Ichiro Katayama  Tetsuji Naka
Affiliation:1. Laboratory of Immune Signal, National Institute of Biomedical Innovation, Ibaraki, Japan;2. Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Japan;3. Department of Surgery, Osaka University Graduate School of Medicine, Suita, Japan;4. Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan
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.
Keywords:apoptosis  JAK/STAT  malignant melanoma  p53  suppressor of cytokine signalling‐1
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