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Regulation of c-fos and c-jun Protooncogene Expression by the Ca2+- ATPase Inhibitor Thapsigargin
Axel Schonthal, Jeff Sugarman, Joan Heller Brown, Michael R. Hanley and James R. Feramisco
Proceedings of the National Academy of Sciences of the United States of America
Vol. 88, No. 16 (Aug. 15, 1991), pp. 7096-7100
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/2357628
Page Count: 5
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Thapsigargin, a non-phorbol-ester-type tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase. We used this drug to analyze the involvement of Ca2+ and Ca2+-ATPases in the control of growth- and transformation-related genes. Here we show that treatment of mouse NIH 3T3 fibroblasts with thapsigargin induced rapid expression of the c-fos and c-jun protooncogenes. Inhibition or depletion of protein kinase C partially diminished the c-fos but not the c-jun response. Furthermore, thapsigargin could synergize with the tumor promoter phorbol 12-myristate 13-acetate to induce c-fos but not c-jun. However, thapsigargin had no effect on basal or phorbol ester-induced protein kinase C activity. Our results indicate that Ca2+ is a potent second messenger that controls expression of growth- and transformation-related genes. Since inhibition of the endoplasmic reticulum Ca2+-ATPase results in a strong induction of these genes, our data suggest that this Ca2+ pump may act as a negative regulator of cell growth.
Proceedings of the National Academy of Sciences of the United States of America © 1991 National Academy of Sciences