Restoration of p53 gene function in 12-O-tetradecanoylphorbor 13-acetate-resistant human leukemia K562/TPA cells

Int J Oncol. 2003 Jan;22(1):81-6.

Abstract

The human leukemia K562 cell line does not express wild-type p53 protein. Due to the loss of one p53 allele and an insertion mutation in exon 5 of the other allele resulting in a frameshift mutation, K562 cells express a truncated p53 protein of 148 amino acids. A human leukemia phorbol ester-resistant subline, K562/TPA, is cross-resistant to some anticancer agents. A remarkable difference in cell cycle progression at G1/S phase was observed in the synchronised K562/TPA cells as compared with K562 cells. Southern blot and DNA sequence analysis revealed no mutation in exon 5 of the p53 gene in K562/TPA cells. p21Cip1 expression was also restored in K562/TPA cells confirming that the reversal of this p53 gene mutation restored wild-type p53 function in these cells. This is a unique report describing reversal of p53 gene mutation by drugs. This was associated with the expression of wild-type p53 mRNA and protein in K562/TPA cells. The K562/TPA cell line may provide a very useful tool for the investigation of the relationship between p53 status and chemosensitization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Southern
  • Cell Cycle
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / analysis
  • Drug Resistance, Neoplasm*
  • Genes, p53 / physiology*
  • Humans
  • K562 Cells / drug effects*
  • K562 Cells / metabolism
  • Karyotyping
  • Sequence Analysis, DNA
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Tumor Suppressor Protein p53 / analysis

Substances

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