Overexpression of an α1H (Cav3.2) T-type Calcium Channel during Neuroendocrine Differentiation of Human Prostate Cancer Cells

• Published in: The Journal of biological chemistry 2002-03, Vol.277 (13), p.10824-10833
• Main Authors: Mariot, Pascal, Vanoverberghe, Karine, Lalevée, Nathalie, Rossier, Michel F., Prevarskaya, Natalia
• Format: Article
• Language: English
• Subjects: Biochemistry, Molecular Biology; Cancer; Genomics; Human health and pathology; Life Sciences; Urology and Nephrology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M108754200

Neuroendocrine differentiation of prostate epithelial cells is usually associated with an increased aggressivity and invasiveness of prostate tumors and a poor prognosis. However, the molecular mechanisms involved in this process remain poorly understood. We have investigated the possible expression of voltage-gated calcium channels in human prostate cancer epithelial LNCaP cells and their modulation during neuroendocrine differentiation. A small proportion of undifferentiated LNCaP cells displayed a voltage-dependent calcium current. This proportion and the calcium current density were significantly increased during neuroendocrine differentiation induced by long-term treatments with cyclic AMP permeant analogs or with a steroid-reduced culture medium. Biophysical and pharmacological properties of this calcium current suggest that it is carried by low-voltage activated T-type calcium channels. Reverse transcriptase-PCR experiments demonstrated that only a single type of LVA calcium channel mRNA, an α1H calcium channel mRNA, is expressed in LNCaP cells. Quantitative real-time reverse transcriptase-PCR revealed that α1H mRNA was overexpressed during neuroendocrine differentiation. Finally, we show that this calcium channel promotes basal calcium entry at resting membrane potential and may facilitate neurite lengthening. This voltage-dependent calcium channel could be involved in the stimulation of mitogenic factor secretion and could therefore be a target for future therapeutic strategies.