par Thebault, Stéphanie;Flourakis, Matthieu;Vanoverberghe, Karine;Vandermoere, Franck;Roudbaraki, Morad;Lehen'kyi, V'yacheslav;Slomianny, Christian;Beck, Benjamin ;Mariot, Pascal;Bonnal, Jean-Louis;Mauroy, Brigitte;Shuba, Yaroslav;Capiod, Thierry;Skryma, Roman;Prevarskaya, Natalia
Référence Cancer research, 66, 4, page (2038-2047)
Publication Publié, 2006-02
Référence Cancer research, 66, 4, page (2038-2047)
Publication Publié, 2006-02
Article révisé par les pairs
Résumé : | 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 alpha1-adrenergic receptors (alpha1-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 alpha1-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. |