The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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The TREK2 Channel Is Involved in the Proliferation of 253J Cell, a Human Bladder Carcinoma Cell

  • Park, Kyung-Sun (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology) ;
  • Han, Min Ho (Department of Biochemistry, Dongeui University College of Oriental Medicine) ;
  • Jang, Hee Kyung (Department of Physiology, College of Medicine, Chungbuk National University) ;
  • Kim, Kyung-A (Department of Biomedical Engineering, College of Medicine, Chungbuk National University) ;
  • Cha, Eun-Jong (Department of Biomedical Engineering, College of Medicine, Chungbuk National University) ;
  • Kim, Wun-Jae (Department of Urology, College of Medicine, Chungbuk National University) ;
  • Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine) ;
  • Kim, Yangmi (Department of Physiology, College of Medicine, Chungbuk National University)
  • Received : 2013.10.08
  • Accepted : 2013.11.19
  • Published : 2013.12.30
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Abstract

Bladder cancer is the seventh most common cancer in men that smoke, and the incidence of disease increases with age. The mechanism of occurrence has not yet been established. Potassium channels have been linked with cell proliferation. Some two-pore domain $K^+$ channels (K2P), such as TASK3 and TREK1, have recently been shown to be overexpressed in cancer cells. Here we focused on the relationship between cell growth and the mechanosensitive K2P channel, TREK2, in the human bladder cancer cell line, 253J. We confirmed that TREK2 was expressed in bladder cancer cell lines by Western blot and quantitative real-time PCR. Using the patch-clamp technique, the mechanosensitive TREK2 channel was recorded in the presence of symmetrical 150 mM KCl solutions. In 253J cells, the TREK2 channel was activated by polyunsaturated fatty acids, intracellular acidosis at -60 mV and mechanical stretch at -40 mV or 40 mV. Furthermore, small interfering RNA (siRNA)-mediated TREK2 knockdown resulted in a slight depolarization from $-19.9mV{\pm}0.8$ (n=116) to $-8.5mV{\pm}1.4$ (n=74) and decreased proliferation of 253J cells, compared to negative control siRNA. 253J cells treated with TREK2 siRNA showed a significant increase in the expression of cell cycle boundary proteins p21 and p53 and also a remarkable decrease in protein expression of cyclins D1 and D3. Taken together, the TREK2 channel is present in bladder cancer cell lines and may, at least in part, contribute to cell cycle-dependent growth.

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References

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