Abstract
BackgroundOvarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK), accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K+) channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression.ObjectivesTo determine the expression of the potassium channels Eag and HERG in ovarian cancer tissue and to assess their role in cell proliferation.MethodsThe expression of Eag and HERG potassium channels was examined in an ovarian cancer tissue microarray. Their role in cell proliferation was investigated by blocking voltage-gated potassium channels in an ovarian cancer cell line (SK-OV-3).ResultsWe show for the first time that high expression of Eag channels in ovarian cancer patients is significantly associated with poor survival (P = 0.016) unlike HERG channel expression where there was no correlation with survival. There was also a significant association of Eag staining with high tumour grade (P = 0.014) and presence of residual disease (P = 0.011). Proliferation of SK-OV-3 cells was significantly (P < 0.001) inhibited after treatment with voltage gated K+ channel blockers.ConclusionThis novel finding demonstrates a role for Eag as a prognostic marker for survival in patients with ovarian cancer.
Highlights
Ovarian cancer is the second most common malignancy of the female genital tract in the United Kingdom (UK)
We show for the first time that high expression of Eag channels in ovarian cancer patients is significantly associated with poor survival (P = 0.016) unlike HERG channel expression where there was no correlation with survival
Eag and HERG potassium channels are expressed in the SK-OV-3 cell line There is demarcated staining of the plasma membrane of cells incubated with Eag antibody while nuclear staining was seen when the cells were incubated with HERG antibody (n = 3; Figure 2A and 2B, higher magnification is shown in inset)
Summary
Ovarian cancer is the second most common malignancy of the female genital tract in the UK. Ovarian cancer mortality rates in the UK since the early 1970 s, have remained stable at ~10-12 per 100,000 women. This is in part due to the asymptomatic nature of the disease with most women presenting at a late stage [1]. Ovarian cancer is the second most common cancer of the female genital tract in the United Kingdom (UK), accounting for 6% of female deaths due to cancer. This cancer is associated with poor survival and there is a need for new treatments in addition to existing chemotherapy to improve survival. Potassium (K+) channels have been shown to be overexpressed in various cancers where they appear to play a role in cell proliferation and progression
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