Expression of memory, differentiation, and repression of c-myc and p53 genes in human RD/TE-671 cells induced by a ureido-derivative of pyridine (UDP-4).
Human TE-671 cells have been used to study several aspects of neuroectodermal tumors in culture. Since the human TE-671 cell lines has been re-identified as a rhabdomyosarcoma (RD) rather than a medulloblastoma due to the presence of muscle-type nicotinic acetylcholine receptors, we re-investigated the nature of RD/TE-671 cells and characterized their differentiation induced by 2-(3-ethylureido)-6-methylpyridine (UDP-4), a potent inducer of differentiation of neoplastic cells. RD cells were also used for comparative studies. RD/TE-671 cells exposed to UDP-4 were differentiated irreversibly into postmitotic cells expressing mainly neurofilaments and, to a lesser extent, myoid proteins. In contrast to RD cells that expressed preferentially myoid and not neurofilament proteins (NFPs) upon treatment with UDP-4, differentiated RD/TE-671 cells exhibited characteristic dendritic processes and expressed NFPs (NFP68, NFP160, and NFP200), parvalbumin (calcium-binding protein), and neuron-specific enolase, as well as a small amount of vimentin and desmin. In addition, differentiated RD/TE-671 cells expressed memory for differentiation and underwent an irreversible limitation of proliferation, loss of clonogenic potential, selective repression of c-myc and p53 proto-oncogenes, and changes in cell surface architecture. Treatment of RD/ TE-671 cells with nerve growth factor or epidermal growth factor in the presence of UDP-4 did not alter the phenotype of differentiated cells, whereas co-treatment with 12-O-tetradecanoylphorbol-13-acetate and UDP-4 enhanced morphological differentiation. Therefore, we conclude that: (a) RD/TE-671 cells challenged with UDP-4 express memory to differentiate in the absence of inducer; (b) in contrast to RD cells, RD/TE-671 cells appear to be multipotent cells of neuroectodermal origin capable of differentiation into cells expressing neuronal rather than myoid proteins upon treatment with UDP-4; and (c) differentiation of RD/TE-671 cells leads to selective cessation of cell proliferation and repression of c-myc and p53 proto-oncogenes.
Pappas
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IS
Department of Pharmaceutical Sciences, School of Health Sciences, Aristotle University of Thessaloniki, Greece.
Sophianos
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D
Tzartos
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Tsiftsoglou
A S
AS
D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D007156:Immunologic Memory; D009414:Nerve Growth Factors / Q000494:pharmacology; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000235:genetics* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology*; D012097:Repressor Proteins / Q000502:physiology*; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
D004273:DNA, Neoplasm; D009414:Nerve Growth Factors; D011725:Pyridines; D012097:Repressor Proteins; C102877:2-(3-ethylureido)-6-methylpyridine; D004815:Epidermal Growth Factor; D014508:Urea; D013755:Tetradecanoylphorbol Acetate