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Alterations in the regulatory volume decrease (RVD) and swelling-activated Cl- current associated with neuroendocrine differentiation of prostate cancer epithelial cells.

L Lemonnier·R Lazarenko·Y Shuba·S Thebault·M Roudbaraki·G Lepage·N Prevarskaya·R Skryma
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Abstract

Neuroendocrine (NE) differentiation of prostate epithelial/basal cells is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. Here we report for the first time on alterations in regulatory volume decrease (RVD) and its key determinant, swelling-activated Cl- current (I(Cl,swell)), associated with NE differentiation of androgen-dependent LNCaP prostate cancer epithelial cells. NE-differentiating regimens, namely, chronic cAMP elevation or androgen deprivation, resulted in generally augmented I(Cl,swell) and enhanced RVD. This occurred as a result of both the increased endogenous expression of ClC-3, which is a volume-sensitive Cl- channel involved, as we show, in I(Cl,swell) in LNCaP (lymph-node carcinoma of the prostate) cells and the weaker negative I(Cl,swell) control from Ca2+ entering via store-dependent pathways. The changes in the RVD of NE-differentiated cells generally mimicked those reported for Bcl-2-conferred apoptotic resistance. Our results suggest that strengthening the mechanism that helps to maintain volume constancy may contribute to better survival rates of apoptosis-resistant NE cells.

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AndrogensApoptosisCalciumCell DifferentiationCell SizeChloride ChannelsEpithelial CellsHumansMaleNeoplasms, Hormone-DependentPatch-Clamp TechniquesProstatic NeoplasmsProto-Oncogene Proteins c-bcl-2Up-RegulationJournal ArticleResearch Support, Non-U.S. Gov't

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L Lemonnier, R Lazarenko, Y Shuba, S Thebault, M Roudbaraki, G Lepage, N Prevarskaya, R Skryma. 2005. Alterations in the regulatory volume decrease (RVD) and swelling-activated Cl- current associated with neuroendocrine differentiation of prostate cancer epithelial cells.. https://doi.org/10.1677/erc.1.00898

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