Activation of NF-kappaB mediates the PMA-induced differentiation of K562 cells.
The role of NF-kappaB during the PMA-induced megakaryocytic differentiation of K562 cells was investigated using K562 cells transfected with each or both subunits of NF-kappaB. The NF-kappaB subunit-transfected cells have shown much higher sensitivity to PMA-induced differentiation than their parental cells. This result was consistent with the findings that PMA-stimulated activities of NF-kappaB were markedly increased in the NF-kappaB subunit-transfected cells in comparison with their parental cells and PMA-induced differentiation was enhanced by pretreatment with IkappaB-alpha antisense oligonucleotide in the NF-kappaB subunit-transfected cells. Meanwhile, there were basically no difference in the basal and PMA-stimulated MAP kinase activities among the parental and NF-kappaB subunit-transfected cells, respectively. However, PMA-induced differentiation was blocked by pretreatment with PD98059, a specific inhibitor of MEK, in both parental and NF-kappaB-transfected cells. Therefore, these results suggest that during the PMA-induced megakaryocytic differentiation of K562 cells, NF-kappaB works downstream of MAP kinase, or that activation of both NF-kappaB and MAP kinase pathways is involved.
Pusan Cancer Research Center, Pusan National University, South Korea. kcdshbw@hyowon.pusan.ac.kr
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Kang
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Han
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Kim
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Lee
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Chung
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D002273:Carcinogens / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D020014:K562 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D004791:Enzyme Inhibitors; D005419:Flavonoids; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one