Variation of T-type calcium channel protein expression affects cell division of cultured tumor cells.
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.
Panner
Amith
A
Department of Neurological Surgery and The Brain Tumor Research Center, University of California San Francisco, San Francisco, CA 94115, USA. apanner@cc.ucsf.edu
Cribbs
Leanne L
LL
Zainelli
Gina M
GM
Origitano
Thomas C
TC
Singh
Sanjay
S
Wurster
Robert D
RD
D000818:Animals; D001254:Astrocytoma / Q000378:metabolism; D015153:Blotting, Western; D019556:COS Cells; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D002455:Cell Division / Q000502:physiology*; D002522:Chlorocebus aethiops; D006801:Humans; D020748:Mibefradil / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D020748:Mibefradil