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Anticancer Res ; 33(4): 1401-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23564779

RESUMO

BACKGROUND/AIMS: 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. MATERIALS AND 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. CONCLUSION: 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.


Assuntos
Apoptose , Proliferação de Células , Neoplasias Ovarianas/patologia , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Ácidos Araquidônicos/farmacologia , Western Blotting , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/metabolismo , Canais de Potássio de Domínios Poros em Tandem/antagonistas & inibidores , Análise Serial de Tecidos , Células Tumorais Cultivadas , Adulto Jovem
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