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タイトル: | Live imaging of transforming growth factor-β activated kinase 1 activation in Lewis lung carcinoma 3LL cells implanted into syngeneic mice and treated with polyinosinic: Polycytidylic acid |
著者: | Takaoka, Saori Kamioka, Yuji Takakura, Kanako Baba, Ai Shime, Hiroaki Seya, Tsukasa Matsuda, Michiyuki https://orcid.org/0000-0002-5876-9969 (unconfirmed) |
著者名の別形: | 高岡, 沙織 上岡, 裕治 松田, 道行 |
キーワード: | Förster (or fluorescence) resonance energy transfer in vivo imaging Polyinosinic:polycytidylic acid (PolyI:C) TGF-β activated kinase 1 Two-photon excitation microscopy |
発行日: | May-2016 |
出版者: | John Wiley & Sons Australia, Ltd |
誌名: | Cancer Science |
巻: | 107 |
号: | 5 |
開始ページ: | 644 |
終了ページ: | 652 |
抄録: | Transforming growth factor-β activated kinase 1 (TAK1) has been shown to play a crucial role in cell death, differentiation, and inflammation. Here, we live-imaged robust TAK1 activation in Lewis lung carcinoma 3LL cells implanted into the s.c. tissue of syngeneic C57BL/6 mice and treated with polyinosinic:polycytidylic acid (PolyI:C). First, we developed and characterized a Förster resonance energy transfer-based biosensor for TAK1 activity. The TAK1 biosensor, named Eevee-TAK1, responded to stress-inducing reagents such as anisomycin, tumor necrosis factor-α, and interleukin1-β. The anisomycin-induced increase in Förster resonance energy transfer was abolished by the TAK1 inhibitor (5z)-7-oxozeaenol. Activity of TAK1 in 3LL cells was markedly increased by PolyI:C in the presence of macrophages. 3LL cells expressing Eevee-TAK1 were implanted into mice and observed through imaging window by two-photon excitation microscopy. During the growth of tumor, the 3LL cells at the periphery of the tumor showed higher TAK1 activity than the 3LL cells located at the center of the tumor, suggesting that cells at the periphery of the tumor mass were under stronger stress. Injection of PolyI:C, which is known to induce regression of the implanted tumors, induced marked and homogenous TAK1 activation within the tumor tissues. The effect of PolyI:C faded within 4 days. These observations suggest that Eevee-TAK1 is a versatile tool to monitor cellular stress in cancer tissues. The TAK1 FRET biosensor enables visualization of the stress response in vivo. |
著作権等: | © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
URI: | http://hdl.handle.net/2433/215165 |
DOI(出版社版): | 10.1111/cas.12923 |
PubMed ID: | 26931406 |
出現コレクション: | 学術雑誌掲載論文等 |
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