p53-independent induction of WAF1/CIP1 in human leukemia cells is correlated with growth arrest accompanying monocyte/macrophage differentiation

Cancer Res. 1995 Feb 1;55(3):668-74.


The p53 tumor suppressor gene plays a role in controlling a G1 phase checkpoint. The WAF1/CIP1 gene with encodes p21WAF1/CIP1 protein, an inhibitor of cyclin-dependent kinases, is a downstream mediator of p53 function. We examined expression of the WAF1/CIP1 gene and its relationship to growth arrest and differentiation in p53-null human leukemic cell lines. We show that p53-independent induction of WAF1/CIP1 occurs in human leukemia cells treated with 12-O-tetradecanoylphorbol-13-acetate, okadaic acid, or IFN-gamma but not with retinoic acid, vitamin D3, or DMSO. Furthermore, WAF1/CIP1 induction correlates with growth arrest associated with monocyte-macrophage differentiation. The present studies support the idea that WAF1/CIP1 gene expression can be regulated through multiple mechanisms, suggesting that strategies may be designed to restore the G1 checkpoint controls in p53-null cells by targeting these p53-independent mechanisms of WAF1/CIP1 induction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Northern
  • Cell Cycle
  • Cell Differentiation / drug effects
  • Cell Division
  • Cell Line
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis*
  • DNA, Neoplasm / biosynthesis
  • Electroporation
  • Flow Cytometry
  • Gene Expression*
  • Genes, p53*
  • Granulocytes / cytology
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Monocytes / cytology
  • Protein Kinase Inhibitors
  • Tetradecanoylphorbol Acetate
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA, Neoplasm
  • Protein Kinase Inhibitors
  • Tumor Suppressor Protein p53
  • Tetradecanoylphorbol Acetate