| PKC Pathway and ERK/MAPK Pathway Are Required for Induction of Cyclin D1 and p21Waf1 during 12-o-tetradecanoylphorbol 13-acetate-induced Differentiation of Myeloleukemia Cells (2006) | |||||||||||
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| Treatment of human promyelocytic leukemia cell HL60 with12-o-tetradecanoylphorbol 13-acetate (TPA) induces growth arrest, differentiationtowards the monocyte/macrophage lineage, and expression of cell cycle-regulatinggenes cyclin D1 and p21Waf1. First, we demonstrated that p21Waf1 expression wasincreased by TPA in other leukemia cell lines also, including THP-1, U937, and KG-1,which differentiate into monocytes/macrophages by TPA. Secondly, we demonstratedthe signal transduction pathways of cyclin D1 and p21Waf1 expressions in TPA-treatedHL60 cells. Induction of cyclin D1 expression in TPA-treated HL60 cells was inhibitedwith protein kinase C (PKC) inhibitor bisindolylmaleimide I and mitogen activatedprotein kinase kinase (MEK) inhibitor PD98059. Induction of p21Waf1 expression inTPA-treated HL60 cells was inhibited with PKC inhibitor bisindolylmaleimide I andGo6976, MEK inhibitor PD98059, and p38 mitogen-actibated protein kinase (MAPK)inhibitor SB202190. Thus, cyclin D1 and p21Waf1 expressions are considered to beinduced via PKC and extracellular signal-regulated kinase/mitogen-activated proteinkinase (MAPK/ERK) pathways in TPA-treated HL60 cells. The upregulation of p21Waf1seems to play a critical role in TPA-induced cell differentiation by suppressing cyclindependent kinase activity , while the upregulation of cyclin D1 seems to be compensatedby p21Waf1. | |||||||||||
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