Variation of T-type calcium channel protein expression affects cell division of cultured tumor cells

Cell Calcium. 2005 Feb;37(2):105-19. doi: 10.1016/j.ceca.2004.07.002.

Abstract

In this study we investigated the T-type calcium channel and its involvement in the cell division of U87MG cultured glioma cells and N1E-115 neuroblastoma cells. Using Western blot analysis, we found that expression of both alpha1G and alpha1H subunits of the T-type calcium channel decreased during conditions associated with a decrease in proliferation as evidenced by increased expression of cyclin D1, a marker for non-proliferating cells. Both serum starvation and application of mibefradil, a selective T-type calcium channel antagonist, resulted in a 50% decrease in the expression of alpha1G and alpha1H and a 700-900% increase in levels of cyclin D1 in U87MG and N1E-115 cells, respectively. Furthermore, overexpression of the alpha1H subunit resulted in a two-fold increase in cell proliferation compared to control cultures or cultures receiving an empty vector. In contrast, blocking expression of the alpha1G subunit using antisense oligonucleotides lead to a 70% decrease in proliferation of U87MG and N1E-115 cells compared to control cultures or cultures receiving a scrambled oligonucleotide. Our findings suggest that proliferation of U87MG glioma cells and N1E-115 is regulated by T-type calcium channel expression.

MeSH terms

  • Animals
  • Astrocytoma / metabolism
  • Blotting, Western
  • COS Cells
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, T-Type / biosynthesis
  • Calcium Channels, T-Type / drug effects
  • Calcium Channels, T-Type / genetics*
  • Cell Division / physiology*
  • Chlorocebus aethiops
  • Humans
  • Mibefradil / pharmacology
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Mibefradil