Transcriptional regulation of early growth response genes in FOS-expressing PC-12 cells.
Deregulated c-fos expression in the rat pheochromocytoma cell line, PC-12, causes pronounced downregulation of nerve growth factor (NGF)-induced c-fos and c-jun activation, accompanied by a block in NGF-induced differentiation of PC-12 cells. The FOS-expressing PC-12 cells were exposed to diverse agents such as NGF, epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), dibutyryl cyclic adenosine 3',5' monophosphate (db cAMP), and Ca-ionophore; and the expression of egr-1, c-fos, c-jun, jun-B, and jun-D was analyzed. Pronounced downregulation of c-fos, c-jun, and--to a lesser extent--jun-B was observed on treatment with NGF, bFGF, db cAMP, and Ca-ionophore, whereas EGF-induced activation of these early response genes was not inhibited in FOS-expressing PC-12 cells. Ca-ionophore- and db cAMP-induced egr-1 activation in PC-12 fos cells was completely inhibited. Both parent and PC-12 fos cells expressed similar high basal levels of jun-D, whose expression was the least regulatable by all of these agents. Transfection of fos promoter-chloramphenicol acetyltransferase (promoter-CAT) plasmid into these stable FOS-expressing PC-12 cells revealed that these effects are exerted at the fos promoter level.
Ito
E
E
Department of Molecular Genetics, Roche Research Center, Nutley, New Jersey 07110.
Nomura
N
N
Narayanan
R
R
D000310:Adrenal Gland Neoplasms / Q000473:pathology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D005810:Multigene Family; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D010673:Pheochromocytoma / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004268:DNA-Binding Proteins; D006133:Growth Substances; D007378:Interleukins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D003994:Bucladesine; D066246:ErbB Receptors; D009955:Ornithine Decarboxylase