Induction of in vitro differentiation of mouse embryonal carcinoma (F9) cells by inhibitors of topoisomerases.
To investigate the possible involvement of topoisomerases in embryonal differentiation, we examined the effect of topoisomerase inhibitors on the in vitro differentiation of mouse embryonal carcinoma F9 cells. We found that camptothecin, teniposide (VM-26), or genistein, specific inhibitors of topoisomerases, induced morphological as well as biochemical changes (production of tissue plasminogen activator, synthesis of laminin, and disappearance of stage-specific embryonic antigen 1) specific to F9 cell differentiation. Since these changes were indistinguishable from those observed in F9 differentiation induced by retinoic acid (plus dibutyryl cyclic AMP), it was suggested that inhibition of cellular topoisomerase activities triggered F9 cell differentiation into parietal endoderm-like cells in the same manner as retinoic acid (plus dibutyryl cyclic AMP). Experiments using differentiation-resistant mutant F9 cell lines, however, indicated that the molecular cascade involved in topoisomerase inhibitor-induced differentiation involves different steps from those functioning in the retinoic acid-induced differentiation cascade.
Institute of Applied Microbiology, University of Tokyo, Japan.
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K
Kondo
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Tsuneizumi
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T
Watanabe
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M
Oishi
D000818:Animals; D015153:Blotting, Western; D002166:Camptothecin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004264:DNA Topoisomerases, Type I / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D019833:Genistein; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D007797:Laminin / Q000096:biosynthesis; D016256:Lewis X Antigen / Q000378:metabolism; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013713:Teniposide / Q000494:pharmacology; D013724:Teratoma / Q000378:metabolism / Q000473:pathology*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis; D059004:Topoisomerase I Inhibitors; D014212:Tretinoin / Q000494:pharmacology
D007529:Isoflavones; D007797:Laminin; D016256:Lewis X Antigen; D059004:Topoisomerase I Inhibitors; D014212:Tretinoin; D013713:Teniposide; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D010959:Tissue Plasminogen Activator; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin