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 neuroect odermal tumors in culture. Since the human TE-671 cell line has been r e-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 the ir 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 cont rast to RD cells that expressed preferentially myoid and not neurofila ment proteins (NFPs) upon treatment with UDP-4, differentiated RD/TE-6 71 cells exhibited characteristic dendritic processes and expressed NF Ps (NFP68, NFP160, and NFP200), parvalbumin (calcium-binding protein), and neuron-specific enolase, as well as a small amount of vimentin an d desmin, In addition, differentiated RD/TE-671 cells expressed memory for differentiation and underwent an irreversible limitation of proli feration, loss of clonogenic potential, selective repression of c-myc and p53 proto-oncogenes, and changes in cell surface architecture, Tre atment 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 differ entiated cells, whereas cotreatment with 12-O-tetradecanoylphorbol-13- acetate and UDP-4 enhanced morphological differentiation, Therefore, w e conclude that: (a) RD/TE-671 cells challenged with UDP-4 express mem ory to differentiate in the absence of inducer; (b) in contrast to RD cells, RD/TE-671 cells appear to be multipotent cells of neuroectoderm al origin capable of differentiation into cells expressing neuronal ra ther than myoid proteins upon treatment with UDP-4; and (c) differenti ation of RD/TE-671 cells leads to selective cessation of cell prolifer ation and repression of c-myc and p53 protooncogenes.