Differential Role of Transient Receptor Potential Channels in Ca2+ Entry and Proliferation of Prostate Cancer Epithelial Cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancer Research Année : 2006

Differential Role of Transient Receptor Potential Channels in Ca2+ Entry and Proliferation of Prostate Cancer Epithelial Cells

Stephanie Thebault
  • Fonction : Auteur
Matthieu Flourakis
  • Fonction : Auteur
Karine Vanoverberghe
  • Fonction : Auteur
Franck Vandermoere
  • Fonction : Auteur
Morad Roudbaraki
  • Fonction : Auteur
Christian Slomianny
  • Fonction : Auteur
Benjamin Beck
  • Fonction : Auteur
Pascal Mariot
Jean-Louis Bonnal
  • Fonction : Auteur
Brigitte Mauroy
  • Fonction : Auteur
Yaroslav Shuba
  • Fonction : Auteur
Thierry Capiod
  • Fonction : Auteur
Roman Skryma
  • Fonction : Auteur
Natalia Prevarskaya
  • Fonction : Auteur

Résumé

Abstract One major clinical problem with prostate cancer is the cells' ability to survive and proliferate upon androgen withdrawal. Because Ca2+ is central to growth control, understanding the mechanisms of Ca2+ homeostasis involved in prostate cancer cell proliferation is imperative for new therapeutic strategies. Here, we show that agonist-mediated stimulation of α1-adrenergic receptors (α1-AR) promotes proliferation of the primary human prostate cancer epithelial (hPCE) cells by inducing store-independent Ca2+ entry and subsequent activation of nuclear factor of activated T cells (NFAT) transcription factor. Such an agonist-induced Ca2+ entry (ACE) relied mostly on transient receptor potential canonical 6 (TRPC6) channels, whose silencing by antisense hybrid depletion decreased both hPCE cell proliferation and ACE. In contrast, ACE and related growth arrest associated with purinergic receptors (P2Y-R) stimulation involved neither TRPC6 nor NFAT. Our findings show that α1-AR signaling requires the coupled activation of TRPC6 channels and NFAT to promote proliferation of hPCE cells and thereby suggest TRPC6 as a novel potential therapeutic target. (Cancer Res 2006; 66(4): 2038-47)

Dates et versions

hal-04122845 , version 1 (08-06-2023)

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Citer

Stephanie Thebault, Matthieu Flourakis, Karine Vanoverberghe, Franck Vandermoere, Morad Roudbaraki, et al.. Differential Role of Transient Receptor Potential Channels in Ca2+ Entry and Proliferation of Prostate Cancer Epithelial Cells. Cancer Research, 2006, 66 (4), pp.2038-2047. ⟨10.1158/0008-5472.CAN-05-0376⟩. ⟨hal-04122845⟩

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