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  • TRPV6 channel controls prostate cancer cell proliferation via Ca(2+)/NFAT-dependent pathways
  • Lehen'kyi V; Flourakis M; Skryma R; Prevarskaya N
  • Oncogene 2007[Nov]; 26 (52): 7380-5
  • 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.
  • |*Cell Proliferation[MESH]
  • |Apoptosis[MESH]
  • |Calcium Channels/genetics/*metabolism[MESH]
  • |Calcium Signaling[MESH]
  • |Calcium/*metabolism[MESH]
  • |Enzyme Inhibitors/pharmacology[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |NFATC Transcription Factors/*metabolism[MESH]
  • |Prostatic Neoplasms/genetics/*metabolism[MESH]
  • |S Phase/physiology[MESH]
  • |Signal Transduction[MESH]
  • |TRPV Cation Channels/genetics/*metabolism[MESH]
  • |Thapsigargin/pharmacology[MESH]
  • |Tumor Cells, Cultured[MESH]





  • *{{pmid17533368}}
    *<b>[http://www.kidney.de/mlpefetch.php?search=17533368 TRPV6 channel controls prostate cancer cell proliferation via Ca(2+)/NFAT-dependent pathways ]</b> Oncogene 2007; 26(52) ; 7380-5 Lehen'kyi V; Flourakis M; Skryma R; Prevarskaya N

        *17533368*

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    Oncogene

    7380 52.26 2007