Calcium functions as a transcriptional and mitogenic repressor in Syrian hamster embryo cells: roles of intracellular pH and calcium in controlling embryonic cell differentiation and proliferation.
We have investigated the role played by the growth and differentiation factor (GDF)-induced calcium ion second messenger signal in the control of cellular differentiation and proliferation in Syrian hamster embryo (SHE) cells. Blocking the platelet-derived growth factor (PDGF)-induced calcium ion signal with either extracellular/intracellular acidification or pharmacological agents resulted in increased immediate early gene expression and mitogenesis. The increase in immediate early gene expression resulted from a change in the level of immediate early gene transcription and not immediate early gene mRNA stability. Analysis of the promoter elements that control immediate early gene expression indicated that the calcium ion effect is mediated through the CaRE/CRE and AP1 promoter elements. The calcium signal-mediated reduction in PDGF A/B-stimulated SHE cell immediate early gene expression resulted in a reduction in PDGF A/B-induced cellular proliferation. These results demonstrate that in SHE cells, calcium functions to suppress mitogen-induced proliferation at the level of immediate early gene expression, an effect related to the control of cellular proliferation and differentiation by GDFs through the calcium ion second messenger.
Isfort
R J
RJ
CP&RSD/HSD, Procter & Gamble Company, Miami Valley Laboratories, Cincinnati, Ohio 45239-8707, USA.
Cody
D B
DB
Stuard
S B
SB
Ridder
G M
GM
LeBoeuf
R A
RA
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein; D004622:Embryo, Mammalian / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017781:Genes, Immediate-Early / Q000502:physiology; D016762:Genes, fos / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D008647:Mesocricetus; D008934:Mitogens / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D018808:Transcription Factor AP-1; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D002110:Caffeine; D002118:Calcium