Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement

Bidaux, Gabriel; Roudbaraki, Morad; Merle, Carole; Crépin, Alexandre; Delcourt, Philippe; Slomianny, Christian; Thebault, Stéphanie; Bonnal, J; Benahmed, Mohamed; Cabon, Florence; Mauroy, Brigitte; Prevarskaya, Natalia

doi:10.1677/erc.1.00969

Cited by 144 publications

(149 citation statements)

References 38 publications

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“…These results indicate that TRPM8 is an important determiner of Ca 2+ homoeostasis in prostate epithelial cells, and may be a potential drug target for the management of PC. However, in this study, we found that the increased expression of TRPM8 in androgen-independent PC-3 cells induced cell cycle arrest at the G 0 /G 1 stage, as opposed to functioning as an essential component for cell survival as reported earlier [11,12], or for promoting the proliferation of PC-3 cells. Similarly, a report by Altuwaijri et al [17] has shown that dihydrotestosterone at a concentration of 0.001-10 nmol L −1 induces cell cycle arrest or inhibits proliferation of PC-3-AR cells, which overexpress heterologous AR.…”

Section: Discussionsupporting

confidence: 37%

“…Moreover, although remaining at moderate levels in a normal prostate, TRPM8 expression significantly increases in PC cells. Despite a growing number of studies, the npg precise role of TRPM8 in the prostate remains unclear, although it has been suggested to be involved in the secretion functions of the prostate, and in the regulation of proliferation and/or apoptosis [11,12].…”

Section: Discussionmentioning

confidence: 99%

“…Antagonist experiments using capsazepine and TRPM8 expression-silencing experiments using siRNA [11,12] suggested that the Ca 2+ influx mediated by TRPM8 plays an essential role in cellular Ca 2+ homoeostasis in LNCaP cells and is involved in cell survival. These results indicate that TRPM8 is an important determiner of Ca 2+ homoeostasis in prostate epithelial cells, and may be a potential drug target for the management of PC.…”

Section: Discussionmentioning

confidence: 99%

“…Bidaux et al [11] also showed that in PC cell lines, and in primary cultures of normal, hyperplasic and cancerous prostate epithelial cells, TRPM8 was a target gene of the androgen receptor (AR). TRPM8 expressionsilencing experiments using small interference RNA (siRNA) suggested that Ca 2+ influx through the TRPM8 channel plays an essential role in cellular Ca 2+ homoeostasis in prostate epithelial cells and is involved in cell survival [12].…”

Section: Camentioning

confidence: 99%

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Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells

Yang¹,

Wang²,

Wang³

et al. 2009

Asian J Androl

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We investigated the effects of transient receptor potential M8 (TRPM8) channel on the proliferation and motility of androgen-independent prostate cancer PC-3 cells. After being permanently transfected with an empty vector and cDNA encoding the TRPM8 protein, cells were analysed for cell cycle distribution and motility using flow cytometry and scratch assay. Immunocytochemistry and Ca 2+ imaging analysis revealed the overexpression of functional TRPM8 channel on both endoplasmic reticulum and plasma membrane of PC-3-TRPM8 cells. Cell cycle distribution and scratch assay analysis revealed that TRPM8 induced cell cycle arrest at the G 0 /G 1 stage (P < 0.05) and facilitated the cell apoptosis induced by starvation (P < 0.05). Furthermore, TRPM8 inhibited the migration of PC-3-TRPM8 cells (P < 0.01) through the inactivation of focal-adhesion kinase. It appears that TRPM8 was not essential for the survival of PC-3 cells; however, the overexpression of TRPM8 had negative effects on the proliferation and migration of PC-3 cells. Thus, TRPM8 and its agonists may serve as important targets for the treatment of prostate cancer.

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Section: Discussionsupporting

confidence: 37%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Camentioning

confidence: 99%

See 2 more Smart Citations

Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells

Yang¹,

Wang²,

Wang³

et al. 2009

Asian J Androl

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“…Primary PCa epithelial cells (hPCE) were obtained and cultured as described earlier (Bidaux et al, 2005).…”

Section: Cell Culturementioning

confidence: 99%

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

et al. 2009

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Accumulating data point to K þ channels as relevant players in controlling cell cycle progression and proliferation of human cancer cells, including prostate cancer (PCa) cells. However, the mechanism(s) by which K þ channels control PCa cell proliferation remain illusive. In this study, using the techniques of molecular biology, biochemistry, electrophysiology and calcium imaging, we studied the expression and functionality of intermediate-conductance calcium-activated potassium channels (IK Ca1 ) in human PCa as well as their involvement in cell proliferation. We showed that IK Ca1 mRNA and protein were preferentially expressed in human PCa tissues, and inhibition of the IK Ca1 potassium channel suppressed PCa cell proliferation. The activation of IK Ca1 hyperpolarizes membrane potential and, by promoting the driving force for calcium, induces calcium entry through TRPV6, a cation channel of the TRP (Transient Receptor Potential) family. Thus, the overexpression of the IK Ca1 channel is likely to promote carcinogenesis in human prostate tissue.

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Expression of the cold thermoreceptor TRPM8 in rodent brain thermoregulatory circuits

Ordás

Hernández-Ortego

Vara

et al. 2019

J of Comparative Neurology

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The cold-and menthol-activated ion channel transient receptor potential channel subfamily M member 8 (TRPM8) is the principal detector of environmental cold in mammalian sensory nerve endings. Although it is mainly expressed in a subpopulation of peripheral sensory neurons, it has also been identified in non-neuronal tissues. Here, we show, by in situ hybridization (ISH) and by the analysis of transgenic reporter expression in two different reporter mouse strains, that TRPM8 is also expressed in the central nervous system. Although it is present at much lower levels than in peripheral sensory neurons, we found cells expressing TRPM8 in restricted areas of the brain, especially in the hypothalamus, septum, thalamic reticular nucleus, certain cortices and other limbic structures, as well as in some specific nuclei in the brainstem. Interestingly, positive fibers were also found traveling through the major limbic tracts, suggesting a role of TRPM8-expressing central neurons in multiple aspects of thermal regulation, including autonomic and behavioral thermoregulation. Additional ISH experiments in rat brain demonstrated a conserved pattern of expression of this ion channel between rodent species. We confirmed the functional activity of this channel in the mouse brain using electrophysiological patch-clamp recordings of septal neurons. These results open a new window in TRPM8 physiology, guiding further efforts to understand potential roles of this molecular sensor within the brain.

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Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement

Cited by 144 publications

References 38 publications

Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells

Effects of TRPM8 on the proliferation and motility of prostate cancer PC-3 cells

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry

Expression of the cold thermoreceptor TRPM8 in rodent brain thermoregulatory circuits

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