並列タイトル等ユビキリン２は低酸素ストレスに耐性を示すことで骨肉腫の増殖を促進させる
一般注記type:Thesis
Ubiquilin 2 (UBQLN2), a member of the ubiquitin-like protein family (ubiquilins), maintains protein homeostasis. Although UBQLN2 has been implicated in the pathogenesis of neurodegenerative diseases, it is also associated with malignant tumors. Therefore, we examined whether UBQLN2 plays a role in human osteosarcoma. The human osteosarcoma cell line MG63 was transfected with UBQLN2 siRNA and cultured under hypoxic conditions. The rat osteosarcoma cell line COS1NR was inoculated into Fischer 344 rats, followed by injection of UBQLN2 siRNA with atelocollagen. An immunohistochemical analysis of UBQLN2 was performed using 34 cases of human high-grade osteosarcomas, and metastasis-free survival was estimated by the Kaplan-Meier method. Silencing of UBQLN2 by siRNA transfection under hypoxia led to activation of JNK and p38, resulting in induction of apoptosis in the osteosarcoma cell line MG63. Injection of UBQLN2 siRNA suppressed tumor growth in the rat osteosarcoma model, followed by apoptosis induction. The immunohistochemical examination revealed that high UBQLN2 expression was significantly associated with the unfavorable metastasis-free survival of osteosarcoma patients. UBQLN2 plays an important role in resistance to hypoxic stress and enhances tumor progression in osteosarcoma. UBQLN2 may be a new molecular target for chemotherapeutics and a useful clinicopathological marker in human osteosarcoma.
博士（医学）・甲第637号・平成27年5月28日
Copyright © Spandidos Publications 2015
本文のリンク：http://dx.doi.org/10.3892/or.2015.3788
identifier:Oncology reports Vol.33 No.4 p.1799-1806(2015.04)
identifier:1021335X
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3070
identifier:Oncology reports, 33(4): 1799-1806
DOIinfo:doi/10.3892/or.2015.3788
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