naa a22 4500 510764495 CHVBK 20180411083151.0 cr unu---uuuuu 180411e20131101xx s 000 0 eng 10.1007/s12094-013-1022-4 doi (NATIONALLICENCE)springer-10.1007/s12094-013-1022-4 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 [Elektronische Daten] [A. Innamaa, L. Jackson, V. Asher, G. van Schalkwyk, A. Warren, A. Keightley, D. Hay, A. Bali, H. Sowter, R. Khan] Purpose: 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 96h 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. Federación de Sociedades Españolas de Oncología (FESEO), 2013 Potassium channels nationallicence TREK-1 nationallicence TREK-2 nationallicence Ovarian cancer nationallicence Expression nationallicence Apoptosis nationallicence Innamaa A. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut Jackson L. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut Asher V. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut van Schalkwyk G. Department of Histopathology, Royal Derby Hospital, Uttoxeter Road, DE22 3NE, Derby, UK aut Warren A. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut Keightley A. Department of Obstetrics and Gynaecology, Royal Derby Hospital, Uttoxeter Road, DE22 3NE, Derby, UK aut Hay D. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut Bali A. Department of Obstetrics and Gynaecology, Royal Derby Hospital, Uttoxeter Road, DE22 3NE, Derby, UK aut Sowter H. University of Derby, Kedleston Road, DE22 1GB, Derby, UK aut Khan R. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut Clinical and Translational Oncology Springer Milan 15/11(2013-11-01), 910-918 1699-048X 15:11<910 2013 15 12094 https://doi.org/10.1007/s12094-013-1022-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12094-013-1022-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Innamaa A. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut NATIONALLICENCE 700 1- Jackson L. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut NATIONALLICENCE 700 1- Asher V. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut NATIONALLICENCE 700 1- van Schalkwyk G. Department of Histopathology, Royal Derby Hospital, Uttoxeter Road, DE22 3NE, Derby, UK aut NATIONALLICENCE 700 1- Warren A. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut NATIONALLICENCE 700 1- Keightley A. Department of Obstetrics and Gynaecology, Royal Derby Hospital, Uttoxeter Road, DE22 3NE, Derby, UK aut NATIONALLICENCE 700 1- Hay D. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut NATIONALLICENCE 700 1- Bali A. Department of Obstetrics and Gynaecology, Royal Derby Hospital, Uttoxeter Road, DE22 3NE, Derby, UK aut NATIONALLICENCE 700 1- Sowter H. University of Derby, Kedleston Road, DE22 1GB, Derby, UK aut NATIONALLICENCE 700 1- Khan R. School of Graduate Entry Medicine and Health, University of Nottingham, Uttoxeter Road, DE22 3DT, Derby, UK aut NATIONALLICENCE 773 0- Clinical and Translational Oncology Springer Milan 15/11(2013-11-01), 910-918 1699-048X 15:11<910 2013 15 12094 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer