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- Title
Up-regulation of Kv7.1 channels in thromboxane A-induced colonic cancer cell proliferation.
- Authors
Shimizu, Takahiro; Fujii, Takuto; Takahashi, Yuji; Takahashi, Yuta; Suzuki, Tomoyuki; Ukai, Masashi; Tauchi, Katsunori; Horikawa, Naoki; Tsukada, Kazuhiro; Sakai, Hideki
- Abstract
Thromboxane A (TXA) 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 A (STA), a stable analogue of TXA, 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, TXB, an inactive metabolite of TXA, had no effects on expression level and function of Kv7.1. A TXA receptor antagonist (SQ29548) and an inhibitor of cAMP-dependent protein kinase (Rp-8-Br-MB-cAMPS) inhibited STA-induced increases in both Kv7.1 expression and chromanol 293B-sensitive K currents. Interestingly, STA-stimulated proliferation of colonic cancer cells was inhibited by chromanol 293B. These results suggest that Kv7.1 channels are involved in the TXA-induced cancer cell proliferation and that they are up-regulated by the TXA receptor-mediated cAMP pathway.
- Subjects
GENETIC regulation; THROMBOXANES; CANCER cell proliferation; GENE expression; ION channels; COLON cancer treatment; COLON cancer prognosis; PROTEIN kinases; CYCLIC adenylic acid
- Publication
Pflügers Archiv: European Journal of Physiology, 2014, Vol 466, Issue 3, p541
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-013-1341-x