Cooperative effect of antisense-Rb and antisense-p53 oligomers on the extension of life span in human diploid fibroblasts, TIG-1

Biochem Biophys Res Commun. 1991 Aug 30;179(1):528-34. doi: 10.1016/0006-291x(91)91403-y.


Normal human diploid fibroblasts, TIG-1, which have a replicative life span of about 62 population doublings (PD), tended to senesce after about 50 PD with a gradual decrease in sensitivity to serum. Treatment of TIG-1 cells with the antisense-Rb oligomer, which completely depleted the retinoblastoma susceptibility gene product (RB), extended life span by about 10 PD. Treatment with the antisense-p53 oligomer alone had no effect; however, cotreatment with the antisense-Rb oligomer further potentiated the extension and the increased sensitivity to serum caused by the antisense-Rb oligomer alone, suggesting that p53 and RB function in separate, yet complementary pathways in signal transduction to senescence. The c-fos expression, which is presumed to be regulated negatively by RB, was not stimulated in partially senescent TIG-1 cells by treatment with the antisense-Rb oligomer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Division / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Codon / genetics
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Genes, Retinoblastoma*
  • Humans
  • Kinetics
  • Molecular Sequence Data
  • Oligonucleotides, Antisense / pharmacology*
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogenes / drug effects
  • Retinoblastoma Protein / genetics*
  • Time Factors
  • Tumor Suppressor Protein p53 / genetics*


  • Codon
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-fos
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Protein-Tyrosine Kinases