This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, L. Articles by Barritt, G. J. Search for Related Content PubMed PubMed Citation Articles by Zhang, L. Articles by Barritt, G. J.

Evidence that TRPM8 Is an Androgen-Dependent Ca²⁺ Channel Required for the Survival of Prostate Cancer Cells

¹ Department of Human Physiology and Centre for Neuroscience and ² Department of Medical Biochemistry, Flinders University, Adelaide, South Australia, Australia

The Ca²⁺-permeable channel TRPM8 is thought to play an important role in the pathophysiology of prostate cancer. We have investigated the intracellular location of TRPM8 and its role as a Ca²⁺-permeable channel in an androgen-responsive and an androgen-insensitive prostate cancer cell line. We report evidence from immunofluorescence experiments that in the androgen-responsive LNCaP cell line, the TRPM8 protein is expressed in the endoplasmic reticulum and plasma membrane, acts as a Ca²⁺-permeable channel (assessed using Fura-2 to measure increases in the cytoplasmic Ca²⁺ concentration) in each of these membranes, and is regulated by androgen. Although TRPM8 was detected in the androgen-insensitive PC-3 cell line, no evidence was obtained for regulation of its expression by androgen. The results of experiments using LNCaP cells, the TRPM8 antagonist capsazepine, and small interference RNA targeted to TRPM8 indicate that TRPM8 is required for cell survival. These results indicate that TRPM8 is an important determinator of Ca²⁺ homeostasis in prostate epithelial cells and may be a potential target for the action of drugs in the management of prostate cancer.

This article has been cited by other articles:

				C. D. Johnson, D. Melanaphy, A. Purse, S. A. Stokesberry, P. Dickson, and A. V. Zholos Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1868 - H1877. [Abstract] [Full Text] [PDF]

				M. Lazzeri, E. Costantini, and M. Porena Review: TRP family proteins in the lower urinary tract: translating basic science into new clinical prospective Therapeutic Advances in Urology, April 1, 2009; 1(1): 33 - 42. [Abstract] [PDF]

				A. S. Sabnis, M. Shadid, G. S. Yost, and C. A. Reilly Human Lung Epithelial Cells Express a Functional Cold-Sensing TRPM8 Variant Am. J. Respir. Cell Mol. Biol., October 1, 2008; 39(4): 466 - 474. [Abstract] [Full Text] [PDF]

				H. Yamamura, S. Ugawa, T. Ueda, A. Morita, and S. Shimada TRPM8 activation suppresses cellular viability in human melanoma Am J Physiol Cell Physiol, August 1, 2008; 295(2): C296 - C301. [Abstract] [Full Text] [PDF]

				L. De Petrocellis, V. Vellani, A. Schiano-Moriello, P. Marini, P. C. Magherini, P. Orlando, and V. Di Marzo Plant-Derived Cannabinoids Modulate the Activity of Transient Receptor Potential Channels of Ankyrin Type-1 and Melastatin Type-8 J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 1007 - 1015. [Abstract] [Full Text] [PDF]

				C. B. Phelps and R. Gaudet The Role of the N Terminus and Transmembrane Domain of TRPM8 in Channel Localization and Tetramerization J. Biol. Chem., December 14, 2007; 282(50): 36474 - 36480. [Abstract] [Full Text] [PDF]

				V. U. Bai, A. Kaseb, S. Tejwani, G. W. Divine, E. R. Barrack, M. Menon, A. B. Pardee, and G. P.-V. Reddy Identification of prostate cancer mRNA markers by averaged differential expression and their detection in biopsies, blood, and urine PNAS, February 13, 2007; 104(7): 2343 - 2348. [Abstract] [Full Text] [PDF]

				F. Mahieu, G. Owsianik, L. Verbert, A. Janssens, H. De Smedt, B. Nilius, and T. Voets TRPM8-independent Menthol-induced Ca2+ Release from Endoplasmic Reticulum and Golgi J. Biol. Chem., February 2, 2007; 282(5): 3325 - 3336. [Abstract] [Full Text] [PDF]

				K. Kiselyov, A. Soyombo, and S. Muallem TRPpathies J. Physiol., February 1, 2007; 578(3): 641 - 653. [Abstract] [Full Text] [PDF]

				B. Nilius, G. Owsianik, T. Voets, and J. A. Peters Transient Receptor Potential Cation Channels in Disease Physiol Rev, January 1, 2007; 87(1): 165 - 217. [Abstract] [Full Text] [PDF]

				F. V. Abeele, A. Zholos, G. Bidaux, Y. Shuba, S. Thebault, B. Beck, M. Flourakis, Y. Panchin, R. Skryma, and N. Prevarskaya Ca2+-independent Phospholipase A2-dependent Gating of TRPM8 by Lysophospholipids J. Biol. Chem., December 29, 2006; 281(52): 40174 - 40182. [Abstract] [Full Text] [PDF]

				I. Derler, M. Hofbauer, H. Kahr, R. Fritsch, M. Muik, K. Kepplinger, M. E. Hack, S. Moritz, R. Schindl, K. Groschner, et al. Dynamic but not constitutive association of calmodulin with rat TRPV6 channels enables fine tuning of Ca2+-dependent inactivation J. Physiol., November 15, 2006; 577(1): 31 - 44. [Abstract] [Full Text] [PDF]

				L. Zhang and G. J Barritt TRPM8 in prostate cancer cells: a potential diagnostic and prognostic marker with a secretory function? Endocr. Relat. Cancer, March 1, 2006; 13(1): 27 - 38. [Abstract] [Full Text] [PDF]

				D. E. Clapham, D. Julius, C. Montell, and G. Schultz International Union of Pharmacology. XLIX. Nomenclature and Structure-Function Relationships of Transient Receptor Potential Channels Pharmacol. Rev., December 1, 2005; 57(4): 427 - 450. [Full Text] [PDF]

				S. Thebault, L. Lemonnier, G. Bidaux, M. Flourakis, A. Bavencoffe, D. Gordienko, M. Roudbaraki, P. Delcourt, Y. Panchin, Y. Shuba, et al. Novel Role of Cold/Menthol-sensitive Transient Receptor Potential Melastatine Family Member 8 (TRPM8) in the Activation of Store-operated Channels in LNCaP Human Prostate Cancer Epithelial Cells J. Biol. Chem., November 25, 2005; 280(47): 39423 - 39435. [Abstract] [Full Text] [PDF]

				B. Nilius, T. Voets, and J. Peters TRP Channels in Disease Sci. Signal., August 2, 2005; 2005(295): re8 - re8. [Abstract] [Full Text] [PDF]

				N. Nadif Kasri, G. Bultynck, J. B. Parys, G. Callewaert, L. Missiaen, and H. De Smedt Suramin and Disulfonated Stilbene Derivatives Stimulate the Ca2+-Induced Ca2+-Release Mechanism in A7r5 Cells Mol. Pharmacol., July 1, 2005; 68(1): 241 - 250. [Abstract] [Full Text] [PDF]

				G Bidaux, M Roudbaraki, C Merle, A Crepin, P Delcourt, C Slomianny, S Thebault, J-L Bonnal, M Benahmed, F Cabon, et al. Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement Endocr. Relat. Cancer, June 1, 2005; 12(2): 367 - 382. [Abstract] [Full Text] [PDF]