TRPV6 potentiates calcium-dependent cell proliferation

Cell Calcium. 2006 Feb;39(2):163-73. doi: 10.1016/j.ceca.2005.10.006. Epub 2005 Dec 13.

Abstract

The Ca(2+) homeostasis within cells controls a diversity of cellular processes including gene transcription, proliferation and apoptosis. Perturbance of Ca(2+) signaling may induce deregulation of cell proliferation and suppression of cell death providing the basis for cancer development. In human prostate cancer, a correlation between the mRNA expression of the Ca(2+) channel TRPV6 and the staging of the cancer has been described. We have analyzed the influence of TRPV6 on cell proliferation within HEK-293 cells. We show that TRPV6 increases cell proliferation of HEK-293 cells in a Ca(2+) dependent manner. The increased proliferation correlates with slightly increased intracellular Ca(2+) levels without interfering with the intrinsic Ca(2+) dependence of HEK-293 cell proliferation. Low doses of econazole inhibit both, TRPV6 dependent Ca(2+) signals and cell proliferation while BTP2, a potent inhibitor of Ca(2+) signals and cell proliferation in T-cells, neither influences TRPV6 dependent Ca(2+) signals nor cell proliferation of HEK-293 cells. Our data demonstrate that TRPV6 increases the rate of Ca(2+) dependent cell proliferation which is a prerequisite for its potential role in tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anilides / pharmacology
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Cell Line
  • Cell Proliferation* / drug effects
  • Cell Survival
  • Econazole / pharmacology
  • Gene Expression
  • Humans
  • Male
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*
  • Thiadiazoles / pharmacology
  • Transfection

Substances

  • 4-methyl-4'-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)-1,2,3-thiadiazole-5-carboxanilide
  • Anilides
  • Calcium Channels
  • Recombinant Proteins
  • TRPV Cation Channels
  • TRPV6 protein, human
  • Thiadiazoles
  • Econazole