title: Expression and prognostic significance of the oncogenic K2P potassium channel KCNK9 (TASK-3) in ovarian carcinoma.
abstract: OBJECTIVE
  The TWIK-related acid sensitive K(+) channel-3 (TASK-3) is an oncogenic potassium channel. We investigated the expression of TASK-3 in human ovaries, examined its prognostic significance, and determined effects of TASK-3 blockers on cell proliferation and apoptosis.
  
  
  METHODS
  Immunofluorescence and western blotting were used to investigate TASK-3 expression in two ovarian cancer cell lines, normal ovarian surface epithelium and cancer. Immunohistochemistry quantified expression in an ovarian cancer tissue microarray. The effect of TASK-3 blocking agents on cell proliferation was investigated with the CellTiter 96® Aqueous Non-Radioactive Cell Proliferation assay and on apoptosis with flow cytometry.
  
  
  RESULTS
  TASK-3 expression was confirmed by immunofluorescence in the SKOV-3 and OVCAR-3 cell lines, normal ovaries (n=4) and ovarian tumours (n=4) and by western blotting in normal ovaries (n=6) and ovarian tumours (n=22). Immunohistochemistry demonstrated immunostaining in 99% of tumours (n=230). Increased immunostaining conferred a survival advantage (p=0.002; median survival of >24 months). TASK-3 blockers caused a significant reduction in cell proliferation and an increase in apoptosis in the SKOV-3 and OVCAR-3 cell lines.
  
  
  CONCLUSIONS
  TASK-3 is expressed in epithelial ovarian cancer, conferring a significant survival advantage on patients with increased expression. TASK-3-modulating agents have a significant effect on cell proliferation and apoptosis. Based on these results, we propose that TASK-3 could prove to be both a novel tumour marker and a new therapeutic target in ovarian cancer, but further investigation is required.
authors.affiliation: School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, Derby, UK.
authors.forename: Anni
authors.initials: A
authors.lastname: Innamaa
authors.forename: Leigh
authors.initials: L
authors.lastname: Jackson
authors.forename: Viren
authors.initials: V
authors.lastname: Asher
authors.forename: Gerhard
authors.initials: G
authors.lastname: Van Shalkwyk
authors.forename: Averil
authors.initials: A
authors.lastname: Warren
authors.forename: Daniel
authors.initials: D
authors.lastname: Hay
authors.forename: Anish
authors.initials: A
authors.lastname: Bali
authors.forename: Heidi
authors.initials: H
authors.lastname: Sowter
authors.forename: Raheela
authors.initials: R
authors.lastname: Khan
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D017209:Apoptosis; D001095:Arachidonic Acids / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors / Q000378:metabolism*; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D001095:Arachidonic Acids; C498655:KCNK9 protein, human; D024683:Potassium Channels, Tandem Pore Domain; C088155:methanandamide