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Differential expression of the long and truncated Hv1 isoforms in breast‐cancer cells
Author(s) -
Ventura Clara,
Leon Ignacio Esteban,
Asuaje Agustin,
Martín Pedro,
Enrique Nicolas,
Núñez Mariel,
Cocca Claudia,
Milesi Verónica
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29719
Subject(s) - gene isoform , differential (mechanical device) , breast cancer , expression (computer science) , cancer cell , biology , focus (optics) , cancer , cancer research , microbiology and biotechnology , genetics , gene , computer science , physics , thermodynamics , optics , programming language
Metabolic reprogramming of cancer cells results in a high production of acidic substances that must be extruded to maintain tumor‐cell viability. The voltage‐gated proton channel (Hv1) mediates highly selective effluxes of hydronium‐ion (H + ) that prevent deleterious cytoplasmic acidification. In the work described here, we demonstrated for the first time that the amino‐terminal–truncated isoform of Hv1 is more highly expressed in tumorigenic breast‐cancer‐cell lines than in nontumorigenic breast cells. With respect to Hv1 function, we observed that pharmacologic inhibition of that channel, mediated by the specific blocker 5‐chloro‐2‐guanidinobenzimidazole, produced a drop in intracellular pH and a decrease in cell viability, both in monolayer and in three‐dimensional cultures, and adversely affected the cell‐cycle in tumorigenic breast cells without altering the cycling of nontumorigenic cells. In conclusion, our results demonstrated that the Hv1 channel could be a potential tool both as a biomarker and as a therapeutic target in breast‐cancer disease.