N18-RE-105 cells: differentiation and activation of p53 in response to glutamate and adriamycin is blocked by SV40 large T antigen tsA58.
Process extension was induced in cells of the N18-RE-105 neuroblastoma-retinal hybrid line by toxic agents, including glutamate and the p53-inducing anticancer agents adriamycin and etoposide. Both adriamycin and glutamate activated p53 as measured by a plasmid transfection assay. It was therefore hypothesized that SV40 large T antigen, which binds p53, would interfere with cellular differentiation. To test this hypothesis, the temperature-sensitive form of SV40 large T was transduced into N18-RE-105 cells by retroviral infection. SV40 large T-infected cells became de-differentiated, grew in tightly-packed colonies, lost expression of neurofilament, and lost the ability to differentiate in response to glutamate and adriamycin. The de-differentiating effect of SV40 large T antigen may be due to binding and inactivation of cellular proteins, such as p53, p107, p130, p300, and retinoblastoma protein, which are important in cellular growth and differentiation. It is suggested that p53 may play a role in cellular differentiation, perhaps under unusual circumstances involving stress or cytotoxicity.
Dillon-Carter
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Section on Preclinical Neuroscience Neuropsychiatry Branch, NIMH Neuroscience Center at St. Elizabeths, 2700 Martin Luther King Ave., Washington, D.C., 20032, USA.
Conejero
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Tornatore
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Poltorak
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Freed
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WJ
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000494:pharmacology*; D017920:Antiporters / Q000037:antagonists & inhibitors*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003553:Cystine / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D006822:Hybrid Cells; D051379:Mice; D016501:Neurites / Q000187:drug effects; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012160:Retina / Q000166:cytology; D013696:Temperature; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D000952:Antigens, Polyomavirus Transforming; D017920:Antiporters; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D016159:Tumor Suppressor Protein p53; D006710:Homocysteine; C007956:homocysteic acid; D018698:Glutamic Acid; D003553:Cystine; D005047:Etoposide; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D004317:Doxorubicin