tretinoin and Neoplasms--Nerve-Tissue

During development, the regulation of expression of the Trk family of tyrosine kinase receptors plays an important role in defining the cellular responses to neurotrophin action. We report here that neurotrophin receptors are differentially expressed in distinct populations of retinoic acid-differentiated P19 cells. TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor, and LNGFR, the low-affinity receptor for all neutrophins, are preferentially expressed in P19-derived neurones. In contrast, retinoic acid induces the expression of TrkA, the high-affinity receptor for nerve growth factor, and of a non-catalytic form of TrkB, in non-neural subsets of differentiated cells. We propose P19 cells as a model system to study the mechanisms controlling the expression of neurotrophin receptors and the responsiveness of developing neurones to a specific neurotrophin.

Topics: Animals; Base Sequence; Blotting, Western; Cell Differentiation; Cells, Cultured; Gene Expression Regulation; Mice; Molecular Sequence Data; Neoplasms, Nerve Tissue; Neurons; Polymerase Chain Reaction; Precipitin Tests; Receptor Protein-Tyrosine Kinases; Receptors, Neurotransmitter; RNA; RNA-Directed DNA Polymerase; Tretinoin; Tumor Cells, Cultured

The effect of dexamethasone on the expression of proteolipid protein (PLP) and myelin-associated glycoprotein (MAG) genes was investigated in rat C6 glioma cells. The steady state level of the respective mRNAs was quantitated by Northern blot analysis. The treatment of cells with dexamethasone transiently upregulated the expression of both genes with peak mRNA levels of approximately 10-fold over control levels occurring at day 3 for the PLP gene and at day 5 for the MAG gene. The effect was directly related to the drug concentration in the range from 10(-9) to 10(-5) M. Combined exposure of the cells to dexamethasone and retinoic acid featured an additive effect on PLP gene expression, whereas MAG gene expression was depressed below detectability level. The dissimilarity in the response of the genes to dexamethasone and retinoic acid supports the contention that the genes are controlled by different mechanisms. Furthermore, the results indicate that the effects of dexamethasone and retinoic acid on the myelin genes are mediated by different regulatory pathways.

Topics: Animals; Blotting, Northern; Dexamethasone; Glioma; Myelin Proteins; Myelin-Associated Glycoprotein; Neoplasms, Nerve Tissue; Nucleic Acid Hybridization; Proteolipids; Rats; Signal Transduction; Tretinoin; Tumor Cells, Cultured; Up-Regulation

The histogenesis of Ewing's sarcoma remains unknown. Recent studies have suggested a relationship to an unusual form of childhood neural tumor, often termed peripheral neuroepithelioma or primitive neuroectodermal tumor. Five Ewing's sarcoma tumor cell lines were studied for evidence of a neural phenotype. Under normal culture conditions, no morphologic evidence of neural differentiation was detected. Treatment with retinoic acid, an agent known to induce marked neural differentiation in neuroblastoma, had no demonstrable effect. Treatment with either cyclic AMP or TPA, in contrast, induced pronounced morphologic evidence of neural differentiation. Cells developed elongate processes with varicosities by phase-contrast microscopy; filaments, microtubules, and uraniffin-positive dense core granules were present by electron microscopy. Three neural markers (NSE, NFTP, and cholinesterase) were absent or barely detectable in untreated cells, but became abundant after treatment. These results provide convincing evidence for a neural histogenesis of Ewing's sarcoma. They also suggest a close relationship between Ewing's sarcoma and peripheral neural tumors, including the chest wall tumor described by Askin, but only a distant relationship to neuroblastoma.

Topics: Adolescent; Adult; Animals; Bone Neoplasms; Cell Differentiation; Cells, Cultured; Cholinesterases; Cyclic AMP; Cytoskeletal Proteins; Female; Humans; Male; Mice; Mice, Nude; Microscopy, Electron; Neoplasms, Nerve Tissue; Nerve Growth Factors; Phosphopyruvate Hydratase; Sarcoma, Ewing; Tretinoin