Transcriptional regulation of early growth response genes in FOS-expressing PC-12 cells.

AUTOR(ES)

Ito, E

RESUMO

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.

Documentos Relacionados

• Nerve growth factor stimulates protein tyrosine phosphorylation in PC-12 pheochromocytoma cells.
• Nerve growth factor modulates the drug sensitivity of neurotransmitter release from PC-12 cells.
• Regulation of protein kinase C activity in neuronal differentiation induced by the N-ras oncogene in PC-12 cells.
• Nerve growth factor employs multiple pathways to induce primary response genes in PC12 cells.
• Nerve growth factor stimulates the hydrolysis of glycosylphosphatidylinositol in PC-12 cells: a mechanism of protein kinase C regulation.