Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
Int J Mol Sci. 2014 Jan 10;15(1):977-93. doi: 10.3390/ijms15010977.
The KCNQ gene family, whose members encode Kv7 channels, belongs to the voltage-gated potassium (Kv) channel group. The roles of this gene family have been widely investigated in nerve and muscle cells. In the present study, we investigated several characteristics of Kv7.5, which is strongly expressed in the canine osteosarcoma cell line, CCL-183. Serum starvation upregulated Kv7.5 expression, and the Kv7 channel opener, flupirtine, attenuated cell proliferation by arresting cells in the G0/G1 phase. We also showed that Kv7.5 knockdown helps CCL-183 cells to proliferate. In an effort to find an endogenous regulator of Kv7.5, we used mithramycin A to reduce the level of the transcription factor Sp1, and it strongly inhibited the induction of Kv7.5 in CCL-183 cells. These results suggest that the activation of Kv7.5 by flupirtine may exert an anti-proliferative effect in canine osteosarcoma. Therefore, Kv7.5 is a possible molecular target for canine osteosarcoma therapy.
KCNQ 基因家族成员编码 Kv7 通道，属于电压门控钾（Kv）通道群。该基因家族的作用已在神经和肌肉细胞中得到广泛研究。在本研究中，我们研究了在犬骨肉瘤细胞系 CCL-183 中强烈表达的 Kv7.5 的几个特性。血清饥饿上调 Kv7.5 的表达，而 Kv7 通道 opener 氟吡汀通过将细胞阻滞在 G0/G1 期来抑制细胞增殖。我们还表明，Kv7.5 的敲低有助于 CCL-183 细胞增殖。为了寻找 Kv7.5 的内源性调节剂，我们使用米托蒽醌 A 降低转录因子 Sp1 的水平，它强烈抑制 CCL-183 细胞中 Kv7.5 的诱导。这些结果表明，氟吡汀激活 Kv7.5 可能在犬骨肉瘤中发挥抗增殖作用。因此，Kv7.5 可能是犬骨肉瘤治疗的潜在分子靶点。
