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

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.
AuthorsV Lehen'kyi, M Flourakis, R Skryma, N Prevarskaya
JournalOncogene (Oncogene) Vol. 26 Issue 52 Pg. 7380-5 (Nov 15 2007) ISSN: 1476-5594 [Electronic] England
PMID17533368 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Calcium Channels
  • Enzyme Inhibitors
  • NFATC Transcription Factors
  • TRPV Cation Channels
  • TRPV6 protein, human
  • Thapsigargin
  • Calcium
Topics
  • Apoptosis
  • Calcium (metabolism)
  • Calcium Channels (genetics, metabolism)
  • Calcium Signaling
  • Cell Proliferation
  • Enzyme Inhibitors (pharmacology)
  • Humans
  • Male
  • NFATC Transcription Factors (metabolism)
  • Prostatic Neoplasms (genetics, metabolism)
  • S Phase (physiology)
  • Signal Transduction
  • TRPV Cation Channels (genetics, metabolism)
  • Thapsigargin (pharmacology)
  • Tumor Cells, Cultured

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