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TRPV6 channel controls prostate cancer cell proliferation via Ca2+/NFAT-dependent pathways

Oncogene volume 26, pages 7380–7385 (2007)Cite this article

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 Ca2+-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 Ca2+ 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 Ca2+ 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 Ca2+ channel in prostate cancer cells may represent a mechanism for maintaining a higher proliferation rate, increasing cell survival and apoptosis resistance as well.

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Acknowledgements

This work was supported by grants from Institut National de la Santé et de la Recherche Médicale, Ministère de l'Education Nationale, Ligue National Contre le Cancer and Institut National du Cancer. V'yacheslav Lehen'kyi was supported by a grant from Institut National du Cancer, Ministère de l'Education Nationale and Regione Nord Pas-de Calais.

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  1. R Skryma and N Prevarskaya: These authors shared senior authorship.

Authors and Affiliations

  1. Inserm, U-800, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France

    V Lehen'Kyi, M Flourakis, R Skryma & N Prevarskaya

  2. Université des Sciences et Technologies de Lille (USTL), Villeneuve d'Ascq, France

    V Lehen'Kyi, M Flourakis, R Skryma & N Prevarskaya

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  1. V Lehen'Kyi
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  2. M Flourakis
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  3. R Skryma
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  4. N Prevarskaya
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Correspondence to N Prevarskaya.

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Lehen'Kyi, V., Flourakis, M., Skryma, R. et al. TRPV6 channel controls prostate cancer cell proliferation via Ca2+/NFAT-dependent pathways. Oncogene 26, 7380–7385 (2007). https://doi.org/10.1038/sj.onc.1210545

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