Spontaneous transformation of an immortalized hepatocyte cell line

Potential role of a nuclear protease

David A. Drubin, Gary Clawson

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In this study, we utilized an in vitro model of spontaneous transformation/progression, an SV40 large T antigen-immortalized rat hepatocyte cell line (designated CWSV14) that is very weakly tumorigenic at low-passage, but acquires a transformed phenotype upon extended passage in cell culture. Here we show that this mid-passage transformation is accompanied by development of aneuploidy and disorganization of the actin cytoskeleton, concomitant with a large increase in a chymotrypsin-like nuclear protease activity which we have previously implicated in chemical transformation of fibroblasts and ras-transformation of hepatocytes. Passage of the CWSV14 cells with AAPF cmk, a relatively selective inhibitor of the nuclear protease activity, abrogates the acquisition of the transformed phenotype and prevents the changes in the actin cytoskeleton. We hypothesize that the nuclear protease may play a role in initiating development of genomic instability, paralleling the archetypical role of proteases in paradigms such as the SOS-type responses in bacteria and yeast.

Original languageEnglish (US)
Pages (from-to)39-48
Number of pages10
JournalCancer Letters
Volume213
Issue number1
DOIs
StatePublished - Sep 15 2004

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Actin Cytoskeleton
Hepatocytes
Peptide Hydrolases
Chymases
Polyomavirus Transforming Antigens
Phenotype
Cell Line
Genomic Instability
Viral Tumor Antigens
Aneuploidy
Protease Inhibitors
Cell Culture Techniques
Fibroblasts
Yeasts
Bacteria
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

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Spontaneous transformation of an immortalized hepatocyte cell line : Potential role of a nuclear protease. / Drubin, David A.; Clawson, Gary.

In: Cancer Letters, Vol. 213, No. 1, 15.09.2004, p. 39-48.

Research output: Contribution to journalArticle

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