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

LEON I; MARTIN P; MILESI V.; ASUAJE A; NUÑEZ, M.; VENTURA C; ENRIQUE N; COCCA C

Braga

Congreso; ISCaM2019 - 6th Annual meeting; 2019

International Society of Cancer Metabolism

The current knowledge indicates that neoplastic transformation is associated 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 without affecting MCF-10A cells. Here, we explore if these differences could be associated with the expression of the N-terminally truncated Hv1 isoform [HV1(S)] that is specifically enriched in malignant B cells resulting in higher proliferation and migration [2]. Experimental: we examined (by western blot and flow cytometry) the expression of the HV1 in the three human breast cell lines. We tested the amount of both isoform [Hv1(L+S)] using a polyclonal antibody which recognize the residues 32-44, present in both isoforms. Then, the large isoform [Hv1(L)] was detected using an antibody that recognize 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