TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.

Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tu...

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Autores principales:	V'yacheslav Lehen'kyi, Maylis Raphaël, Agathe Oulidi, Matthieu Flourakis, Sergii Khalimonchyk, Artem Kondratskyi, Dmitri V Gordienko, Brigitte Mauroy, Jean-Lois Bonnal, Roman Skryma, Natalia Prevarskaya
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/179e9fe891d94c3cb6e0b525824e4109
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spelling	oai:doaj.org-article:179e9fe891d94c3cb6e0b525824e41092021-11-18T06:58:54ZTRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.1932-620310.1371/journal.pone.0016856https://doaj.org/article/179e9fe891d94c3cb6e0b525824e41092011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347289/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tumors. One of the prospective therapeutical agents even used in the first stage clinical trials, 1,25-dihydroxyvitamin D3, was shown to be either unpredictable or inefficient in many cases. We have already shown that TRPV6 calcium channel, which is the direct target of 1,25-dihydroxyvitamin D3 receptor, positively controls prostate cancer proliferation and apoptosis resistance (Lehen'kyi et al., Oncogene, 2007). However, how the known 1,25-dihydroxyvitamin D3 antiproliferative effects may be compatible with the upregulation of pro-oncogenic TRPV6 channel remains a mystery. Here we demonstrate that in low steroid conditions 1,25-dihydroxyvitamin D3 upregulates the expression of TRPV6, enhances the proliferation by increasing the number of cells entering into S-phase. We show that these pro-proliferative effects of 1,25-dihydroxyvitamin D3 are directly mediated via the overexpression of TRPV6 channel which increases calcium uptake into LNCaP cells. The apoptosis resistance of androgen-dependent LNCaP cells conferred by TRPV6 channel is drastically inversed when 1,25-dihydroxyvitamin D3 effects were combined with the successful TRPV6 knockdown. In addition, the use of androgen-deficient DU-145 and androgen-insensitive LNCaP C4-2 cell lines allowed to suggest that the ability of 1,25-dihydroxyvitamin D3 to induce the expression of TRPV6 channel is a crucial determinant of the success or failure of 1,25-dihydroxyvitamin D3-based therapies.V'yacheslav Lehen'kyiMaylis RaphaëlAgathe OulidiMatthieu FlourakisSergii KhalimonchykArtem KondratskyiDmitri V GordienkoBrigitte MauroyJean-Lois BonnalRoman SkrymaNatalia PrevarskayaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e16856 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q V'yacheslav Lehen'kyi Maylis Raphaël Agathe Oulidi Matthieu Flourakis Sergii Khalimonchyk Artem Kondratskyi Dmitri V Gordienko Brigitte Mauroy Jean-Lois Bonnal Roman Skryma Natalia Prevarskaya TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.
description	Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tumors. One of the prospective therapeutical agents even used in the first stage clinical trials, 1,25-dihydroxyvitamin D3, was shown to be either unpredictable or inefficient in many cases. We have already shown that TRPV6 calcium channel, which is the direct target of 1,25-dihydroxyvitamin D3 receptor, positively controls prostate cancer proliferation and apoptosis resistance (Lehen'kyi et al., Oncogene, 2007). However, how the known 1,25-dihydroxyvitamin D3 antiproliferative effects may be compatible with the upregulation of pro-oncogenic TRPV6 channel remains a mystery. Here we demonstrate that in low steroid conditions 1,25-dihydroxyvitamin D3 upregulates the expression of TRPV6, enhances the proliferation by increasing the number of cells entering into S-phase. We show that these pro-proliferative effects of 1,25-dihydroxyvitamin D3 are directly mediated via the overexpression of TRPV6 channel which increases calcium uptake into LNCaP cells. The apoptosis resistance of androgen-dependent LNCaP cells conferred by TRPV6 channel is drastically inversed when 1,25-dihydroxyvitamin D3 effects were combined with the successful TRPV6 knockdown. In addition, the use of androgen-deficient DU-145 and androgen-insensitive LNCaP C4-2 cell lines allowed to suggest that the ability of 1,25-dihydroxyvitamin D3 to induce the expression of TRPV6 channel is a crucial determinant of the success or failure of 1,25-dihydroxyvitamin D3-based therapies.
format	article
author	V'yacheslav Lehen'kyi Maylis Raphaël Agathe Oulidi Matthieu Flourakis Sergii Khalimonchyk Artem Kondratskyi Dmitri V Gordienko Brigitte Mauroy Jean-Lois Bonnal Roman Skryma Natalia Prevarskaya
author_facet	V'yacheslav Lehen'kyi Maylis Raphaël Agathe Oulidi Matthieu Flourakis Sergii Khalimonchyk Artem Kondratskyi Dmitri V Gordienko Brigitte Mauroy Jean-Lois Bonnal Roman Skryma Natalia Prevarskaya
author_sort	V'yacheslav Lehen'kyi
title	TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.
title_short	TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.
title_full	TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.
title_fullStr	TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.
title_full_unstemmed	TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.
title_sort	trpv6 determines the effect of vitamin d3 on prostate cancer cell growth.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/179e9fe891d94c3cb6e0b525824e4109
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TRPV6 determines the effect of vitamin D3 on prostate cancer cell growth.

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