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Updated: Aug 21, 2026

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
13:59

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

Molecular signature of oncogenic ras-induced senescence

Douglas X Mason1, Tonya J Jackson, Athena W Lin

  • 1Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.

Oncogene
|October 19, 2004
PubMed

Insights

Cellular senescence, a stress-induced cell cycle arrest, shares mechanisms between replicative and oncogenic H-ras-induced senescence. Topoisomerase IIalpha and HDAC9 may serve as novel biomarkers for senescent human fibroblasts.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Cellular senescence irreversibly arrests proliferation following significant stress.
  • Replicative senescence, driven by telomere dysfunction, acts as a cancer barrier.
  • Senescence induced by oncogenic H-ras mimics replicative senescence, suggesting a common underlying mechanism.

Purpose of the Study:

  • To investigate the gene expression profile of human diploid fibroblasts undergoing oncogenic H-ras-induced senescence.
  • To compare the gene expression changes in H-ras-induced senescence with replicative senescence.
  • To identify potential novel biomarkers for cellular senescence.

Main Methods:

  • Analysis of gene expression profiles in oncogenic H-ras-induced senescent human diploid fibroblasts.
  • Comparison of gene expression patterns between H-ras-induced and replicative senescent cells.
  • Identification of genes with altered expression under various senescence conditions.

Main Results:

  • Altered gene expression of cell cycle regulators was observed in both H-ras-induced and replicative senescent cells.
  • H-ras-induced senescent cells showed downregulation of G2/M checkpoint control genes.
  • Tetraploid cells arrested in the G1 phase were found in H-ras-induced senescent cells, similar to replicative senescence.

Conclusions:

  • Inactivation of G2/M checkpoints may contribute to senescence and the generation of senescent G1 tetraploid cells.
  • Topoisomerase IIalpha and HDAC9 expression alterations are specifically associated with senescence.
  • Topoisomerase IIalpha and HDAC9 represent potential novel biomarkers for senescent human fibroblasts.

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