title: Expression and effects of modulation of the K2P potassium channels TREK-1 (KCNK2) and TREK-2 (KCNK10) in the normal human ovary and epithelial ovarian cancer.
abstract: OBJECTIVE
  Aberrant expression of potassium (K(+)) channels contributes to cancer cell proliferation and apoptosis, and K(+) channel blockers can inhibit cell proliferation. TREK-1 and -2 belong to the two-pore domain (K2P) superfamily. We report TREK-1 and -2 expression in ovarian cancer and normal ovaries, and the effects of TREK-1 modulators on cell proliferation and apoptosis.
  
  
  METHODS
  The cellular localisation of TREK-1 and -2 was investigated by immunofluorescence in SKOV-3 and OVCAR-3 cell lines and in cultured ovarian surface epithelium and cancer. Channel expression in normal ovaries and cancer was quantified by western blotting. Immunohistochemical analysis demonstrated the association between channel expression and disease prognosis, stage, and grade. TREK-1 modulation of cell proliferation in the cell lines was investigated with the MTS-assay and the effect on apoptosis determined using flow cytometry.
  
  
  RESULTS
  Expression was identified in both cell lines, ovarian cancer (n = 22) and normal ovaries (n = 6). IHC demonstrated positive staining for TREK-1 and -2 in 95.7 % of tumours (n = 69) and 100 % of normal ovaries (n = 9). A reduction in cell proliferation (P < 0.05) was demonstrated at 96 h in SKOV-3 and OVCAR-3 cells incubated TREK-1 modulating agents. Curcumin caused a significant reduction in early apoptosis in SKOV-3 (P < 0.001) and OVCAR-3 (P < 0.0001) cells and a significant increase in late apoptosis in SKOV-3 (P < 0.01) and OVCAR-3 cells (P < 0.0001).
  
  
  CONCLUSIONS
  TREK-1 and -2 are expressed in normal ovaries and ovarian cancer. TREK-1 modulators have a significant effect on cell proliferation and apoptosis. We propose investigation of the therapeutic potential of TREK-1 blockers is warranted.
authors.affiliation: School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, Derby, DE22 3DT, UK, anniinnamaa@yahoo.ie.
authors.forename: A
authors.initials: A
authors.lastname: Innamaa
authors.forename: L
authors.initials: L
authors.lastname: Jackson
authors.forename: V
authors.initials: V
authors.lastname: Asher
authors.forename: G
authors.initials: G
authors.lastname: van Schalkwyk
authors.forename: A
authors.initials: A
authors.lastname: Warren
authors.forename: A
authors.initials: A
authors.lastname: Keightley
authors.forename: D
authors.initials: D
authors.lastname: Hay
authors.forename: A
authors.initials: A
authors.lastname: Bali
authors.forename: H
authors.initials: H
authors.lastname: Sowter
authors.forename: R
authors.initials: R
authors.lastname: Khan
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C503438:KCNK10 protein, human; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D003474:Curcumin