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Differential Role of Transient Receptor Potential Channels in Ca²⁺ Entry and Proliferation of Prostate Cancer Epithelial Cells

¹ Laboratoire de Physiologie Cellulaire, Institut National de la Sante et de la Recherche Medicale and ² Laboratoire de Biologie du Développement, Centre National de la Recherche Scientifique, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, France

Requests for reprints: Stephanie Thebault, Laboratoire de Physiologie Cellulaire, Institut National de la Sante et de la Recherche Medicale EMI 0228, Bâtiment SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France. Phone: 33-3-20-43-40-77; E-mail: stephanie_thebault{at}yahoo.fr.

One major clinical problem with prostate cancer is the cells' ability to survive and proliferate upon androgen withdrawal. Because Ca²⁺ is central to growth control, understanding the mechanisms of Ca²⁺ homeostasis involved in prostate cancer cell proliferation is imperative for new therapeutic strategies. Here, we show that agonist-mediated stimulation of ₁-adrenergic receptors (₁-AR) promotes proliferation of the primary human prostate cancer epithelial (hPCE) cells by inducing store-independent Ca²⁺ entry and subsequent activation of nuclear factor of activated T cells (NFAT) transcription factor. Such an agonist-induced Ca²⁺ entry (ACE) relied mostly on transient receptor potential canonical 6 (TRPC6) channels, whose silencing by antisense hybrid depletion decreased both hPCE cell proliferation and ACE. In contrast, ACE and related growth arrest associated with purinergic receptors (P2Y-R) stimulation involved neither TRPC6 nor NFAT. Our findings show that ₁-AR signaling requires the coupled activation of TRPC6 channels and NFAT to promote proliferation of hPCE cells and thereby suggest TRPC6 as a novel potential therapeutic target. (Cancer Res 2006; 66(4): 2038-47)

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