myelin-basic-protein 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

Malignant peripheral nerve sheath tumor (MPNST) commonly presents a diagnostic challenge and may resemble a variety of other soft tissue neoplasms microscopically. The authors have examined 62 examples of MPNST immunohistochemically, using antibodies to S-100 protein, myelin basic protein (MBP), and Leu-7, all of which are potential neural markers. Sixty-eight percent of all cases expressed at least one of these three determinants, representing a higher rate of immunoreactivity than that seen for single nervous system antigens in previous studies. Conjoint reactivity for S-100/Leu-7, S-100/MBP, and MBP/Leu-7 was seen in 34%, 34%, and 24% of cases, respectively. This coexpression of antigens is important, because none of them in isolation is immunospecific for nerve sheath tumors. In addition, stains for epithelial membrane antigen were reactive in two epithelioid tumors in this series, and eight spindle-cell neoplasms demonstrated desmin positivity. Analyses for cytokeratin, carcinoembryonic antigen, and Factor VIII-related antigen were negative in all cases. These results indicate an overlap between the immunocytochemical attributes of malignant peripheral nerve sheath tumors and other soft tissue sarcomas and emphasize the desirability of assessing multiple neural markers in such cases.

Topics: Antigens; Antigens, Neoplasm; Factor VIII; Histocytochemistry; Humans; Immunoenzyme Techniques; Intermediate Filament Proteins; Membrane Proteins; Mucin-1; Myelin Basic Protein; Neurilemmoma; Peripheral Nervous System Neoplasms; S100 Proteins; von Willebrand Factor