Molecular basis for the cellular senescence program and its application to anticancer therapy

Research output: Contribution to journalReview article

17 Citations (Scopus)

Abstract

Although dysfunctional telomeres and oncogenic or stressful stimuli are known to trigger cellular senescence in normal human diploid cells, the molecules and signaling network involved in the cellular senescence program are not fully understood. We have been trying to identify cellular senescence-inducing factors by various means. First, we screened for an extrinsic signal that can induce cellular senescence in human lung adenocarcinoma cell line A549, and identified transforming growth factor-β (TGF-β) as the cellular senescence-inducing factor. Cancer cells senesced by treatment with TGF-β impaired tumorigenicity both in vitro and in vivo, suggesting that cellular senescence functions as a tumor suppression mechanism. Next, we identified 86 independent senescence-associated genes by subtractive screening using A549-derived cell lines. Thirdly, we established novel cell lines (AST cells) from A549 cells exposed to mild oxidative stress. AST cells demonstrated functional impairment of telomerase due to perturbed subcellular localization of human telomerase reverse transcriptase, suggesting that mild oxidative stress might affect the cell fate of cancer cells. These results should provide insight into the molecular basis of the cellular senescence program.

Original languageEnglish
Pages (from-to)1076-1081
Number of pages6
JournalBioscience, Biotechnology and Biochemistry
Volume70
Issue number5
DOIs
Publication statusPublished - May 29 2006

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Cell Aging
Cells
Oxidative stress
Transforming Growth Factors
Therapeutics
Oxidative Stress
Telomerase
Neoplasms
Tumors
Screening
Telomere
Genes
Diploidy
Molecules
Cell Line
A549 Cells

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

Cite this

Molecular basis for the cellular senescence program and its application to anticancer therapy. / Katakura, Yoshinori.

In: Bioscience, Biotechnology and Biochemistry, Vol. 70, No. 5, 29.05.2006, p. 1076-1081.

Research output: Contribution to journalReview article

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