Search Results
You are looking at 1 - 3 of 3 items for
- Author: N Prevarskaya x
- Refine by access: All content x
Search for other papers by S Humez in
Google Scholar
PubMed
Search for other papers by M Monet in
Google Scholar
PubMed
Search for other papers by G Legrand in
Google Scholar
PubMed
Search for other papers by G Lepage in
Google Scholar
PubMed
Search for other papers by P Delcourt in
Google Scholar
PubMed
Search for other papers by N Prevarskaya in
Google Scholar
PubMed
Neuroendocrine differentiation (NED) has been implicated in prostate cancer progression and hormone-therapy failure. Neuroendocrine cells are non-proliferating and escape apoptotic cell death, although their origin and the causes of their apoptotic resistance have as yet been poorly elucidated. This study demonstrates a new mechanism involved in controlling NED. We report that epidermal growth factor (5–50 ng/ml) promotes neuroendocrine-like differentiation of androgen-independent DU145 prostate cancer cells. This differentiation is associated with an increase in the expression of Neuron Specific Enolase (NSE) and a reduction in cell proliferation and is blocked by inhibiting tyrosine kinase activity with genistein and with compound 56 (C56). An increase in the cAMP level, using dibutryl cAMP (db-cAMP) (1 mM) and isobutylmethylxanthine (100 μM), does not promote NED by itself, but does increase the effect of EGF on NED. In addition, EGF-induced NED protects cells from apoptosis induced with thapsigargin (1 μM) by reducing the thapsigargin-induced cytosolic calcium overload. In order to describe how EGF-induced NED protects cells against thapigargin-induced calcium overload we investigated the spatiotemporal calcium signalling linked to apoptosis. By using thapsigargin in various conditions on DU145 cells and using micro-fluorimetric calcium measurements, we show that depletion of intracellular calcium store induces apoptosis and that the amplitude and duration of the capacitive calcium entry are two apoptosis-modulating parameters. We show that protection against thapsigargin-induced apoptosis conferred by NED is achieved by reducing the amount and the speed of calcium that can be released from calcium pools, as well as modulating the amplitude of the subsequent calcium entry.
Search for other papers by L Lemonnier in
Google Scholar
PubMed
Search for other papers by R Lazarenko in
Google Scholar
PubMed
Search for other papers by Y Shuba in
Google Scholar
PubMed
Search for other papers by S Thebault in
Google Scholar
PubMed
Search for other papers by M Roudbaraki in
Google Scholar
PubMed
Search for other papers by G Lepage in
Google Scholar
PubMed
Search for other papers by N Prevarskaya in
Google Scholar
PubMed
Search for other papers by R Skryma in
Google Scholar
PubMed
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 (ICl,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 ICl,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 ICl,swell in LNCaP (lymph-node carcinoma of the prostate) cells and the weaker negative ICl,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.
Search for other papers by G Bidaux in
Google Scholar
PubMed
Search for other papers by M Roudbaraki in
Google Scholar
PubMed
Search for other papers by C Merle in
Google Scholar
PubMed
Search for other papers by A Crépin in
Google Scholar
PubMed
Search for other papers by P Delcourt in
Google Scholar
PubMed
Search for other papers by C Slomianny in
Google Scholar
PubMed
Search for other papers by S Thebault in
Google Scholar
PubMed
Search for other papers by J-L Bonnal in
Google Scholar
PubMed
Search for other papers by M Benahmed in
Google Scholar
PubMed
Search for other papers by F Cabon in
Google Scholar
PubMed
Search for other papers by B Mauroy in
Google Scholar
PubMed
Search for other papers by N Prevarskaya in
Google Scholar
PubMed
TRPM8 (melastatine-related transient receptor potential member 8), a member of the transient receptor potential (TRP) superfamily of cation channels, has been shown to be a calcium-channel protein. TRPM8 mRNA has also been shown to be overexpressed in prostate cancer and is considered to play an important role in prostate physiology. This study was designed to determine the androgen-regulation mechanisms for TRPM8 mRNA expression and to identify the phenotype of TRPM8-expressing cells in the human prostate. Our findings show that trpm8 gene expression requires a functional androgen receptor. Furthermore, this article argues strongly in favour of the fact that the trpm8 gene is a primary androgen-responsive gene. Single-cell reverse transcriptase PCR and immunohistochemical experiments also showed that the trpm8 gene was mainly expressed in the apical secretory epithelial cells of the human prostate and trpm8 down-regulation occurred during the loss of the apical differentiated phenotype of the primary cultured human prostate epithelial cells. The androgen-regulated trpm8 expression mechanisms are important in understanding the progression of prostate cancer to androgen-independence. These findings may contribute to design a strategy to predict prostate cancer status from the TRPM8 mRNA level. Furthermore, as the TRPM8 channel is localized in human prostate cells, it will be interesting to understand its physiological function in the normal prostate and its potential role in prostate cancer development.
