Expression profiles of p53-, p16(INK4a)-, and telomere-regulating genes in replicative senescent primary human, mouse, and chicken fibroblast cells

Exp Cell Res. 2002 Jan 15;272(2):199-208. doi: 10.1006/excr.2001.5420.


Replicative senescence is known to be an intrinsic mechanism in determining the finite life span of in vitro cultured cells. Since this process is recognized as an evolutionarily conserved mechanism from yeast to mammalian cells, we compared the senescence-associated genetic alterations in the p53, p16(INK4a), and telomere regulatory pathways using replicative senescent human, mouse, and chicken fibroblast cells. Normal human diploid fibroblast (HDF; WI38) and chicken embryonic fibroblast (CEF) cells were shown to have a more extended in vitro proliferative potential than their mouse embryonic fibroblast (MEF) counterpart. In contrast to the HDF and CEF cells, MEF cells were shown to express telomerase mRNA and maintain telomerase activity throughout their in vitro life span. Functional p53 activity was shown to increase in the replicative senescent HDF and CEF cells, but not in replicative senescent MEF cells. On the other hand, there was a gradual elevation of p16(INK4a) expression with increased cell passages which reached a maximum in replicative senescent MEF cells. Taken together, the present study demonstrates that the p53, p16(INK4a), and telomere regulatory functions may be differentially regulated during replicative senescence in human, mouse, and chicken fibroblast cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle Proteins*
  • Cell Division
  • Cells, Cultured
  • Cellular Senescence
  • Chickens
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics*
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • Fibroblasts / cytology
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Proteins*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-mdm2
  • Retinoblastoma Protein / genetics*
  • Telomerase / metabolism
  • Telomere*
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / genetics*


  • CDKN1A protein, human
  • Cdkn1a protein, mouse
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Retinoblastoma Protein
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2
  • Telomerase