TRPV6 channel controls prostate cancer cell proliferation via Ca(2+)/NFAT-dependent pathways

Oncogene. 2007 Nov 15;26(52):7380-5. doi: 10.1038/sj.onc.1210545. Epub 2007 May 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Calcium / metabolism*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Signaling
  • Cell Proliferation*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Male
  • NFATC Transcription Factors / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • S Phase / physiology
  • Signal Transduction
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Thapsigargin / pharmacology
  • Tumor Cells, Cultured


  • Calcium Channels
  • Enzyme Inhibitors
  • NFATC Transcription Factors
  • TRPV Cation Channels
  • TRPV6 protein, human
  • Thapsigargin
  • Calcium