Early transient suppression of c-myb mRNA levels and induction of differentiation in Friend erythroleukemia cells by the [Ca2+]i-increasing agents cyclopiazonic acid and thapsigargin.
Cyclopiazonic acid and thapsigargin, inhibitors of the endoplasmic reticulum Ca2+ pump were shown to elevate [Ca2+]i in Friend erythroleukemia cells, line F4-6, at concentrations of 1-5 microM and 0.5-2 nM, respectively. At the same concentrations, these agents induced a strong suppression of c-myb mRNA levels within 3 h, whereas c-myc expression remained unaffected. The c-myb expression recovered and approached pretreatment levels at 9-12 h of incubation. The decrease in c-myb mRNA was prevented in Ca(2+)-free medium. Treatment of F4-6 cells with EGTA led to a transient increase in c-myb mRNA with the same kinetics as the Ca2+ pump inhibitor-induced suppression, indicating that c-myb expression is bidirectionally regulated by changes in [Ca2+]i. Studies on the differentiation status of F4-6 cells following cyclopiazonic acid or thapsigargin exposure demonstrated a marked increase in beta-globin mRNA synthesis at 60h and in hemoglobin production at 96 h. These results provide further evidence that a rise in the cytosolic Ca2+ concentration is capable, in Friend erythroleukemia cells, of inducing an early transient suppression of c-myb mRNA levels, which is followed by terminal erythroid differentiation.
Schaefer
A
A
Department of Toxicology, Hamburg University Medical School, Federal Republic of Germany.
Magócsi
M
M
Stöcker
U
U
Kósa
F
F
Marquardt
H
H
D000818:Animals; D002118:Calcium / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002454:Cell Differentiation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D016259:Genes, myc; D007211:Indoles / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007211:Indoles; D012333:RNA, Messenger; D013729:Terpenes; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid; D004121:Dimethyl Sulfoxide