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タイトル: | Thioredoxin-interacting protein suppresses bladder carcinogenesis. |
著者: | Nishizawa, Koji Nishiyama, Hiroyuki Matsui, Yoshiyuki Kobayashi, Takashi Saito, Ryoichi Kotani, Hirokazu Masutani, Hiroshi Oishi, Shinya https://orcid.org/0000-0002-2833-2539 (unconfirmed) Toda, Yoshinobu Fujii, Nobutaka Yodoi, Junji Ogawa, Osamu |
著者名の別形: | 松井, 喜之 小川, 修 |
発行日: | 18-Jul-2011 |
出版者: | Oxford University Press |
誌名: | Carcinogenesis |
巻: | 32 |
号: | 10 |
開始ページ: | 1459 |
終了ページ: | 1466 |
抄録: | Thioredoxin-interacting protein (TXNIP), which has a tumor-suppressive function, is underexpressed in some human cancers. The function of TXNIP in vivo in carcinogenesis is not fully understood. Here, we show TXNIP to be downregulated in human bladder cancer according to grade and stage and also that loss of TXNIP expression facilitates bladder carcinogenesis using a mouse bladder cancer model. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer was found in 100% of Txnip knockout (KO) mice at week 8 of 0.025% BBN administration but in only 22% of wild-type (WT) mice at the same point. Among growth stimulators, phospho-extracellular signal-regulated kinase (pERK) expression was stronger during bladder carcinogenesis in Txnip-KO mice than in WT mice. We then evaluated TXNIP's effects on ERK activation through various growth stimulators and their receptors. Overexpression of TXNIP in human bladder cancer cells attenuated pERK expression upon stimulation with stromal cell-derived factor-1 (SDF-1) but not with epidermal growth factor or insulin-like growth factor-1. In Txnip-KO mice, immunohistochemical analysis showed enhanced expression of C-X-C chemokine receptor type 4 (CXCR4), the receptor of SDF-1, and of pERK in urothelial cells during BBN-induced bladder carcinogenesis. Finally, subcutaneous injection of CXCR4 antagonist, TF14016, attenuated pERK in urothelial cells and suppressed bladder carcinogenesis. These data indicate that TXNIP negatively regulates bladder carcinogenesis by attenuating SDF-1-CXCR4-induced ERK activation. This signal transduction pathway can be a potent target in preventing or treating bladder cancer. |
著作権等: | © The Author 2011. Published by Oxford University Press. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/158366 |
DOI(出版社版): | 10.1093/carcin/bgr137 |
PubMed ID: | 21771725 |
出現コレクション: | 学術雑誌掲載論文等 |
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