The influence of SV40 immortalization of human fibroblasts on p53-dependent radiation responses

Manu Kohli, Timothy J. Jorgensen

Research output: Contribution to journalArticle

Abstract

The simian virus 40 large tumor antigen (SV40 Tag) has been ascribed many functions critical to viral propagation, including binding to the mammalian tumor suppressor p53. Recent studies have demonstrated that SV40-transformed murine cells have functional p53. The status of p53 in SV40-immortalized human cells, however, has not been characterized. We have found that in response to ionizing radiation, p53-dependent p21 transactivation activity is present, albeit reduced, in SV40-immortalized cells and that this activity can be further reduced with either dominant negative p53 expression or higher SV40 Tag expression. Furthermore, overexpression of p53 in SV40-immortalized ataxia-telangiectasia (A-T) cells restores p53-dependent p21 induction to typical A-T levels. All SV40-immortalized cell lines exhibited an absence of G1 arrest. Moreover, all SV40-immortalized cell lines exhibited increased apoptosis relative to primary cells in response to ionizing radiation, suggesting that SV40 immortalization results in a unique phenotype with regard to DNA damage responses.

Original languageEnglish (US)
Pages (from-to)168-176
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume257
Issue number1
DOIs
StatePublished - Apr 2 1999
Externally publishedYes

Fingerprint

Fibroblasts
Ionizing radiation
Cells
Neoplasm Antigens
Radiation
Viruses
Simian virus 40
Ionizing Radiation
T-cells
Cell Line
Ataxia Telangiectasia
Tumors
Apoptosis
Transcriptional Activation
DNA Damage
DNA
T-Lymphocytes
Phenotype
Neoplasms

Keywords

  • Apoptosis
  • Cell cycle
  • p21
  • p53
  • SV40

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

The influence of SV40 immortalization of human fibroblasts on p53-dependent radiation responses. / Kohli, Manu; Jorgensen, Timothy J.

In: Biochemical and Biophysical Research Communications, Vol. 257, No. 1, 02.04.1999, p. 168-176.

Research output: Contribution to journalArticle

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