: The N-terminally truncated isoform of Hv1 is overexpressed in tumorigenic human breast cell lines.

VENTURA C; LEON I.E; ASUAJE A; ENRIQUE N

Congreso; 6Th Annual Meeting of International Society of Cancer Metabolism; 2019

The current knowledge indicates that neoplastic transformation is related with a metabolic deregulation and acid overproduction [1]. In breast cancer cells, we proved that voltage-gated proton channel (Hv1) is functionally relevant in basal intracellular pH control. Comparing the effect of Hv1 inhibition in tumorigenic (MCF-7 and MDA-MB-231) and non-tumorigenic (MCF-10A) human breast cells we found, that it induced cycle arrest and cell viabiliy reduction in tumorigenic cells without affecting MCF-10A cells. Here, we explore if these differences could be associated with the expression of a more reactive N-terminally truncated Hv1 isoform [HV1(S)] which is upregulated in malignant B cells [2]. Experimental methods: we examined (by western blot and flow cytometry) the expression of HV1 in the three human breast cell lines. We tested the amount of both isoform [Hv1(L+S)] using a polyclonal antibody which recognizes the residues 32-44 present in both Hv1 isoforms. Then, the large isoform [Hv1(L)] was detected using an antibody that recognizes the residues 1-30 of the N-terminal region present only in the Hv1(L). Results: we found an equal amount of Hv1(L+S) expressed among the three cell lines. However, the expression of Hv1(L) showed a signifcant decrease (44% and 46% in MCF-7 and MDA-MB-231 respectively vs. MCF-10A cells, p