phorbol-12-13-didecanoate and Peripheral-Nervous-System-Neoplasms

Since synthesis of myelin components has been seen to be stimulated by cAMP in both oligodendrocytes and Schwann cells we have begun investigating the specific sequence(s) in the 5' flanking region of the myelin basic protein (MBP) gene that are responsible for the induction of MBP transcription by cAMP. Using stably transfected cell lines containing various deletions of the MBP promoter directing the bacterial chloramphenicol acetyltransferase (CAT) gene we have identified a region of the MBP gene that is inhibitory to stimulation by increased cAMP levels. This inhibition can be overcome by pretreating the cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) for 48 hr. The effects on MBP gene expression modulated by TPA and cAMP involve altered DNA-protein interactions in the 5' end of the MBP promoter. The effect of TPA also appears to be mediated by down-regulation of protein kinase C.

Topics: 1-Methyl-3-isobutylxanthine; Animals; Base Sequence; Binding Sites; Cyclic AMP; Gene Expression Regulation; Molecular Sequence Data; Myelin Basic Protein; Neurilemmoma; Oligodeoxyribonucleotides; Peripheral Nervous System Neoplasms; Phorbol Esters; Promoter Regions, Genetic; Protein Kinase C; Proto-Oncogene Proteins c-jun; Rats; Recombinant Fusion Proteins; Regulatory Sequences, Nucleic Acid; Sequence Deletion; Signal Transduction; Stereoisomerism; Tetradecanoylphorbol Acetate; Transfection; Tumor Cells, Cultured