Thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+)-ATPase, enhances c-fos expression but antagonizes vacuole formation of human hepatoma cells induced by teleocidin.
Teleocidin, a phorbol ester-type tumor promoter, enhanced actin redistribution, vacuole formation and c-fos expression of PLC/PRF/5 hepatoma cells. This tumor promoter also inhibited calcium mobilization induced by epidermal growth factor (EGF). Thapsigargin, a specific inhibitor of endoplasmic reticulum Ca(2+)-ATPase, elevated cytosolic calcium, enhanced c-fos expression and antagonized the vacuole formation induced by teleocidin without interfering with actin redistribution and Lucifer yellow uptake. On the other hand, a calcium ionophore ionomycin elevated both cytosolic Ca2+ and c-fos mRNA but could not antagonize the vacuole formation induced by teleocidin. From these results it was speculated that the Ca2+ leak from the endoplasmic reticulum rather than the elevation of cytosolic Ca2+ appeared to be responsible for the specific inhibition of vacuole formation by thapsigargin.
Tsukamoto
A
A
First Department of Medicine, University of Tokyo, Japan.
Kaneko
Y
Y
Kurokawa
K
K
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002273:Carcinogens / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008235:Lyngbya Toxins / Q000037:antagonists & inhibitors*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000199:Actins; D002273:Carcinogens; D008235:Lyngbya Toxins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D013729:Terpenes; C022176:teleocidins; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium