Suppressor of cytokine signalling‐1 induces significant preclinical antitumor effect in malignant melanoma cells |
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Authors: | Naoko Tagami‐Nagata Satoshi Serada Minoru Fujimoto Atsushi Tanemura Rie Nakatsuka Tomoharu Ohkawara Hiroyuki Murota Tadamitsu Kishimoto Ichiro Katayama Tetsuji Naka |
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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 |
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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. |
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Keywords: | apoptosis JAK/STAT malignant melanoma p53 suppressor of cytokine signalling‐1 |
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