KCNH1 potassium channels are expressed in cervical cytologies from pregnant patients and are regulated by progesterone

Abstract

Potassium voltage-gated channel, subfamily H (eag-related), member 1 (KCNH1) potassium channels are potential tumour markers and cancer therapeutic targets and are up-regulated by oestrogens and human papilloma virus (HPV) oncogenes. However, the role of KCNH1 in normal tissues is poorly understood, and its expression in pregnancy is unknown. We wondered whether KCNH1 channels are expressed in cervical cells from pregnant patients and whether progesterone (P4) regulates KCNH1. The association with HPV was also investigated. KCNH1 protein expression was studied by immunocytochemistry in liquid-based cervical cytologies; 93 samples were obtained from pregnant patients at different trimesters, and 15 samples were obtained from non-pregnant women (controls). The presence ofHPVwas studied by PCR with direct sequencing and nested multiplex PCR. HeLa cervical cancer cells were transfected with human progesterone receptor-B (PR-B) and treated with P4.KCNH1mRNA expression in these cultures was studied by real-time PCR. KCNH1 protein was detected in 100% of the pregnancy samples and in 26% of the controls. We found 18 pregnant patients infected with HPV and detected 14 types ofHPV. There was no association between the percentage of cells expressing KCNH1 and either the presence or type of HPV. P4induced KCNH1 mRNA and protein expression in cells transfected with human PR-B. No regulation of KCNH1 by P4was observed in non-transfected cells. We show for the first time the expression of an ion channel during human pregnancy at different trimesters and KCNH1 regulation by P4in human cells. These data raise a new research field for KCNH1 channels in human tissues.