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Functional expression of voltage-gated sodium channels in primary cultures of human cervical cancer

Abstract:

Cervical cancer (CaC) is the third most frequent cause of death from cancer among women in the world and the first in females of developing countries. Several ion channels are upregulated in cancer, actually potassium channels have been suggested as tumor markers and therapeutic targets for CaC. Voltage-gated sodium channels (VGSC) activity is involved in proliferation, motility, and invasion of prostate and breast cancer cells; however, the participation of this type of channels in CaC has not been explored. In the present study, we identified both at the molecular and electrophysiological level VCSC in primary cultures from human cervical carcinoma biopsies. With the whole cell patch clamp technique, we isolated and identified a voltage-gated Na+ current as the main component of the inward current in all investigated cells. Sodium current was characterized by its kinetics, voltage dependence, sensitivity to tetrodotoxin (TTX) block and dependence to [Na+]o. By analyzing the expression of mRNAs encoding TTX-sensitive Na+ channel α subunits with standard RT-PCR and specific primers, we detected Na v1.2, Nav1.4, Nav1.6, and Nav1.7 transcripts in total RNA obtained from primary cultures and biopsies of CaC. Restriction enzyme analysis of PCR products was consistent with the molecular nature of the corresponding genes. Notably, only transcripts for Na v1.4 sodium channels were detected in biopsies from normal cervix. The results show for the first time the functional expression of VCSC in primary cultures from human CaC, and suggest that these channels might be considered as potential molecular markers for this type of cancer. © 2006 Wiley-Liss, Inc.