Up-regulation of Kv7.1 channels in thromboxane A2-induced colonic cancer cell proliferation

详细信息    查看全文

• 作者：Takahiro Shimizu (1)
  Takuto Fujii (1)
  Yuji Takahashi (1)
  Yuta Takahashi (1)
  Tomoyuki Suzuki (1)
  Masashi Ukai (1)
  Katsunori Tauchi (2)
  Naoki Horikawa (2)
  Kazuhiro Tsukada (2)
  Hideki Sakai (1)
  
• 关键词：K+ channel ; Thromboxane ; Kv7.1 ; Colon ; Cancer ; Proliferation
• 刊名：Pfl篓鹿gers Archiv - European Journal of Physiology
• 出版年：2014
• 出版时间：March 2014
• 年：2014
• 卷：466
• 期：3
• 页码：541-548
• 全文大小：2,727 KB
• 作者单位：Takahiro Shimizu (1)
  Takuto Fujii (1)
  Yuji Takahashi (1)
  Yuta Takahashi (1)
  Tomoyuki Suzuki (1)
  Masashi Ukai (1)
  Katsunori Tauchi (2)
  Naoki Horikawa (2)
  Kazuhiro Tsukada (2)
  Hideki Sakai (1)
  
  1. Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan
  2. Department of Surgery II, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, 930-0194, Japan
  
• ISSN：1432-2013

文摘

Thromboxane A2 (TXA2) is known to stimulate colonic cancer cell proliferation, although the mechanism has not been clarified. In this study, we compared the expression levels of Kv7.1?K+ channels between human colorectal cancer tissue and the accompanying non-tumor mucosa. Kv7.1 proteins were found to be consistently up-regulated in the cancer tissues from different patients. Kv7.1 was also expressed in human colonic cancer cell lines. Treatment of colonic cancer cells with 9,11-epithio-11,12-methano-thromboxane A2 (STA2), a stable analogue of TXA2, significantly increased whole-cell K+ currents sensitive to chromanol 293B, an inhibitor of Kv7.1 channels, in parallel with an increased expression of Kv7.1 proteins. In contrast, TXB2, an inactive metabolite of TXA2, had no effects on expression level and function of Kv7.1. A TXA2 receptor antagonist (SQ29548) and an inhibitor of cAMP-dependent protein kinase (Rp-8-Br-MB-cAMPS) inhibited STA2-induced increases in both Kv7.1 expression and chromanol 293B-sensitive K+ currents. Interestingly, STA2-stimulated proliferation of colonic cancer cells was inhibited by chromanol 293B. These results suggest that Kv7.1 channels are involved in the TXA2-induced cancer cell proliferation and that they are up-regulated by the TXA2 receptor-mediated cAMP pathway.