title: Serum starvation-induced voltage-gated potassium channel Kv7.5 expression and its regulation by Sp1 in canine osteosarcoma cells.
abstract: 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.
authors.affiliation: 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. bohyung2@snu.ac.kr.
authors.forename: Bo Hyung
authors.initials: BH
authors.lastname: Lee
authors.affiliation: 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. pdryu@snu.ac.kr.
authors.forename: Pan Dong
authors.initials: PD
authors.lastname: Ryu
authors.affiliation: 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. leeso@snu.ac.kr.
authors.forename: So Yeong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004285:Dogs; D051656:KCNQ Potassium Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D008926:Plicamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000631:Aminopyridines; D016895:Culture Media, Serum-Free; D051656:KCNQ Potassium Channels; D016329:Sp1 Transcription Factor; C066851:mithramycin A; C034161:flupirtine; D008926:Plicamycin