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TRPV6 channel controls prostate cancer cell proliferation via Ca(2+)/NFAT-dependent pathways.: Role of TRPV6 in prostate cancer

Abstract : The transient receptor potential channel, subfamily V, member 6 (TRPV6), is strongly expressed in advanced prostate cancer and significantly correlates with the Gleason >7 grading, being undetectable in healthy and benign prostate tissues. However, the role of TRPV6 as a highly Ca(2+)-selective channel in prostate carcinogenesis remains poorly understood. Here, we report that TRPV6 is directly involved in the control of prostate cancer cell (LNCaP cell line) proliferation by decreasing: (i) proliferation rate; (ii) cell accumulation in the S-phase of cell cycle and (iii) proliferating cell nuclear antigen (PCNA) expression. We demonstrate that the Ca(2+) uptake into LNCaP cells is mediated by TRPV6, with the subsequent downstream activation of the nuclear factor of activated T-cell transcription factor (NFAT). TRPV6-mediated Ca(2+) entry is also involved in apoptosis resistance of LNCaP cells. Our results suggest that TRPV6 expression in LNCaP cells is regulated by androgen receptor, however, in a ligand-independent manner. We conclude that the upregulation of TRPV6 Ca(2+) channel in prostate cancer cells may represent a mechanism for maintaining a higher proliferation rate, increasing cell survival and apoptosis resistance as well.Oncogene (2007) 26, 7380-7385; doi:10.1038/sj.onc.1210545; published online 28 May 2007.
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https://www.hal.inserm.fr/inserm-00139720
Contributor : Matthieu Flourakis <>
Submitted on : Wednesday, November 28, 2007 - 9:21:37 AM
Last modification on : Thursday, February 21, 2019 - 10:34:03 AM
Long-term archiving on: : Tuesday, April 6, 2010 - 11:36:06 PM

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V'Yacheslav Lehen'Kyi, Matthieu Flourakis, Roman Skryma, Natalia Prevarskaya. TRPV6 channel controls prostate cancer cell proliferation via Ca(2+)/NFAT-dependent pathways.: Role of TRPV6 in prostate cancer. Oncogene, Nature Publishing Group, 2007, 26 (52), pp.7380-5. ⟨10.1038/sj.onc.1210545⟩. ⟨inserm-00139720⟩

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