Published in

American Society for Clinical Investigation, Journal of Clinical Investigation, 6(117), p. 1647-1657

DOI: 10.1172/jci30168

Links

Tools

Export citation

Search in Google Scholar

Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function

Journal article published in 2007 by Gabriel Bidaux, Matthieu Flourakis ORCID, Stéphanie C. Thebault, Alexander Zholos ORCID, Benjamin Beck, Dimitra Gkika, Morad Roudbaraki, Jean-Louis Bonnal, Brigitte Mauroy, Yaroslav Shuba, Roman Skryma, Natalia Prevarskaya
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

Full text: Download

Red circle
Preprint: archiving forbidden
Red circle
Postprint: archiving forbidden
Green circle
Published version: archiving allowed
Upload
Policy details
Data provided by SHERPA/RoMEO

Abstract

In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer (PCa). However, the mechanisms of prostate-specific regulation and functional evolution of TRPM8 during PCa progression remain unclear. Here we show, for the first time to our knowledge, that only secretory mature differentiated human prostate primary epithelial (PrPE) luminal cells expressed functional plasma membrane TRPM8 ((PM)TRPM8) channels. Moreover, PCa epithelial cells obtained from in situ PCa were characterized by a significantly stronger (PM)TRPM8-mediated current than that in normal cells. This (PM)TRPM8 activity was abolished in dedifferentiated PrPE cells that had lost their luminal secretory phenotype. However, we found that in contrast to (PM)TRPM8, endoplasmic reticulum TRPM8 ((ER)TRPM8) retained its function as an ER Ca(2+) release channel, independent of cell differentiation. We hypothesize that the constitutive activity of (ER)TRPM8 may result from the expression of a truncated TRPM8 splice variant. Our study provides insight into the role of TRPM8 in PCa progression and suggests that TRPM8 is a potentially attractive target for therapeutic intervention: specific inhibition of either (ER)TRPM8 or (PM)TRPM8 may be useful, depending on the stage and androgen sensitivity of the targeted PCa.