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J. Biol. Chem., Vol. 283, Issue 15, 10162-10173, April 11, 2008

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CaV3.2 T-type Calcium Channels Are Involved in Calcium-dependent Secretion of Neuroendocrine Prostate Cancer Cells^*

From the INSERM, U800, Laboratoire de Physiologie Cellulaire, Equipe Labellisée par la Ligue contre le Cancer and Université des Sciences et Technologies de Lille, Villeneuve d'Ascq, 59650, France

Because prostate cancer is, in its early stages, an androgen-dependent pathology, treatments aiming at decreasing testosterone plasma concentration have been developed for many years now. However, a significant proportion of patients suffer a relapse after a few years of hormone therapy. The androgen-independent stage of prostate cancer has been shown to be associated with the development of neuroendocrine differentiation. We previously demonstrated that neuroendocrine prostate cancer cells derived from LNCaP cells overexpress CaV3.2 T-type voltage-dependent calcium channels. We demonstrate here using prostatic acid phosphatase as a marker of prostate secretion and FM1-43 fluorescence imaging of membrane trafficking that neuroendocrine differentiation is associated with an increase in calcium-dependent secretion which critically relies on CaV3.2 T-type calcium channel activity. In addition, we show that these channels are expressed by neuroendocrine cells in prostate cancer tissues obtained from patients after surgery. We propose that CaV3.2 T-type calcium channel up-regulation may account for the alteration of secretion during prostate cancer development and that these channels, by promoting the secretion of potential mitogenic factors, could participate in the progression of the disease toward an androgen-independent stage.

Received for publication, August 27, 2007 , and in revised form, January 10, 2008.

^* This work was supported by INSERM, the Ligue Nationale contre le Cancer (Comité du Nord), and the Université of Sciences et Technologies de Lille. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Laboratoire de Physiologie Cellulaire, INSERM U800, Bâtiment SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cédex, France. Tel.: 33-03-20-43-40-77; Fax: 33-03-20-43-40-66; E-mail: Pascal.Mariot{at}univ-lille1.fr.

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