Differentiation induction in human breast tumor cells by okadaic acid and related inhibitors of protein phosphatases 1 and 2A.
Okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, induces differentiation in human MCF-7, AU-565, and MB-231 breast tumor cells. In MCF-7 cells, OA elicited within 5 min an increase in the levels of a set of phosphorylated cellular proteins, within hours expression of the early response genes junB, c-jun, and c-fos, and within days manifestation of differentiation. Differentiation was also induced by two related protein phosphatase inhibitors, but not by an inactive OA derivative or by an inhibitor that penetrates epithelial cells poorly. These results indicate that OA and related agents can induce tumor breast cell differentiation, and this induction is correlated with their ability to inhibit PPH 1 and 2A.
Kiguchi
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Biological and Medical Research Division, Argonne National Laboratory, Illinois 60439.
Giometti
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Chubb
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Fujiki
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Huberman
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D000911:Antibodies, Monoclonal; D001345:Autoradiography / Q000379:methods; D015152:Blotting, Northern; D001943:Breast Neoplasms; D002364:Caseins / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D016762:Genes, fos / Q000187:drug effects*; D016758:Genes, jun / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008387:Marine Toxins; D052998:Microcystins; D019319:Okadaic Acid / Q000031:analogs & derivatives; D015345:Oligonucleotide Probes; D010080:Oxazoles / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011714:Pyrans / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D002364:Caseins; D004988:Ethers, Cyclic; D007527:Isoenzymes; D008387:Marine Toxins; D052998:Microcystins; D015345:Oligonucleotide Probes; D010080:Oxazoles; D010456:Peptides, Cyclic; D010710:Phosphates; D010750:Phosphoproteins; D010761:Phosphorus Radioisotopes; D011714:Pyrans; D019319:Okadaic Acid; C051904:dinophysistoxin 1; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; C057862:cyanoginosin LR; D013755:Tetradecanoylphorbol Acetate