p53-independent induction of p21 (WAF1/CIP1) during differentiation of HL-60 cells by tumor necrosis factor alpha.
We demonstrated that tumor necrosis factor-alpha (TNF-alpha) rapidly and markedly enhances p21 gene and protein expression prior to monocytic differentiation and apoptosis in p53-null HL-60 cells. TNF-alpha induced early small and delayed large peaks of apoptosis at 6 and 48 h of incubation, respectively. At 24 h of incubation, apparent monocytic differentiation of the cells was noted. Down-regulation of c-myc and c-myb and G0/G1 arrest were observed at 6-12 and 36 h, respectively. Actinomycin D markedly inhibited TNF-alpha-induced p21 mRNA expression, suggesting that the p21 gene is induced at the transcriptional level. We confirmed that TNF-alpha induces p53-independent apoptosis in HL-60 cells, which accompanies monocytic differentiation.
Yoshida
K
K
First Department of Internal Medicine, Saitama Medical School, Japan.
Murohashi
I
I
Hirashima
K
K
D002454:Cell Differentiation / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D016158:Genes, p53; D018922:HL-60 Cells; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha