| Co-Investigator(Kenkyū-buntansha) |
NAKASE Takanobu Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (00283755)
MYOUI Akira Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (10263261)
YOSHIKAWA Hideki Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (60191558)
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| Research Abstract |
NFATs (Nuclear factor of activated T cells) are very important transcriptional regulatory factors of signal transduction through T lymphocyte receptors in lymphoid system. A recent experimental study using knock-out mice has demonstrated that one of the NFAT family, NFATp is an important suppressor of chondrogenesis in adult mice, and indicated that it is working as an inhibitory factor for the differentiation and proliferation of human mesenchymal stem cells (MSC) to chondrocytes. Thus, it is suggested that NFATp gene rearrangement might be involved in the oncogenesis and/or development of human chondrosarcomas, and we hypothesized that NFATp could be used as a molecular target for gene therapy in chondrosarcoma, which is a problematic malignant bone tumor because of its resistance against adjuvant chemotherapy and radiation therapy. To investigate the expression of NFATp gene in human chondrosarcomas, we have performed the screening of the expression of NFATp in frozen tumor samples obtained from 10 patients with chondrosarcoma using RT-PCR method However, all the 10 cases showed positive expression of NFATp gene. Moreover, Aoyama et al. from Kyoto University also reported that seven out of 26 cases of human chondrosarcoma showed NFATp gene mutations in 4 exons, but they were only silent mutation or polymorphism, and concluded that NFATp is not implicated in the pathogenesis of chondrosarcoma. From these results, we have changed the strategy of experimental gene therapy for chondrosarcoma from NFATp to the use of herpes simplex virus thymidine kinase (HS V-TK) and chondrocyte-specific type 11 collagen a2 gene (Col11a2) promoter, which is recently cloned by our colleague, Dr Tsumaki, targeting to chondrosarcomas. We have, therefore, designed and made a plasmid vector inserted HSV-TK and Col11a2 promoter, and transfected it into a human chondrosarcoma cell line to perform in vitro and in vivo experimental gene therapy for chondrosarcoma as a further project.
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