Overexpression of an alpha 1H (Cav3.2) T-type calcium channel during neuroendocrine differentiation of human prostate cancer cells.
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 alpha(1H) calcium channel mRNA, is expressed in LNCaP cells. Quantitative real-time reverse transcriptase-PCR revealed that alpha(1H) 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.
Mariot
Pascal
P
Laboratoire de Physiologie Cellulaire, INSERM EPI9938, Bâtiment SN3, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cédex, France. Pascal.Mariot@univ-lille1.fr
Vanoverberghe
Karine
K
Lalevee
Nathalie
N
Rossier
Michel F
MF
Prevarskaya
Natalia
N
D001483:Base Sequence; D020747:Calcium Channels, T-Type / Q000235:genetics*; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D020747:Calcium Channels, T-Type; D017931:DNA Primers; D012333:RNA, Messenger; D000242:Cyclic AMP