Staurosporine resistance accompanies DNA tumor virus-induced immortalization and is independent of the expression and activities of ERK1, ERK2, cyclin A, cyclin-dependent kinase (cdk) 2, and cdk4

Ted Chang, Ongkar Khalsa, Hong Wang, Mu En Lee, Robert Schlegel

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Staurosporine, a potent protein kinase inhibitor, has been shown to arrest the growth of a number of normal cell types in the G1 phase of the cell cycle, while having little effect on several transformed lines. We wished to determine whether increased resistance to staurosporine was a common feature of virus-immortalized human cells and whether this phenotype was an early event following the expression of SV40 tumor antigens. Human foreskin keratinocytes immortalized by the SV40 DNA tumor virus displayed an increased resistance to staurosporine-induced growth arrest when compared with normal parental cells, as has been seen in human diploid fibroblasts. Keratinocytes immortalized by human papillomaviruses, or by just the human papillomavirus E6 and E7 oncogenes, were also staurosporine resistant, suggesting that this phenotype often accompanies the immortalization of human cells by DNA tumor viruses. Acquisition of staurosporine resistance was a late event during immortalization, because precrisis human diploid fibroblasts that expressed the SV40 large T and small t antigens were not resistant to staurosporine. The same parental cells that were fully immortalized by SV40 were resistant. Staurosporine resistance was not the result of increased activities and/or expression of cyclin A, cyclin- dependent kinase (cdk) 2, cdk4, or the mitogen-activated kinases ERK1 and ERK2. Although increased activities and/or expression of cyclin A and cdk2 and cdk4 proteins, but not ERK1 or ERK2, were associated with immortalization, similar increases were found in staurosporine-sensitive precrisis cells expressing SV40 tumor antigens.

Original languageEnglish
Pages (from-to)361-372
Number of pages12
JournalCell Growth and Differentiation
Volume7
Issue number3
StatePublished - Mar 1996

Keywords

  • Antigens, Polyomavirus Transforming/analysis
  • Calcium-Calmodulin-Dependent Protein Kinases/metabolism
  • Cell Cycle
  • Cell Division/drug effects
  • Cell Line, Transformed
  • Cell Transformation, Viral/physiology
  • Cyclin-Dependent Kinases/metabolism
  • Cyclins/metabolism
  • Diploidy
  • Drug Resistance
  • Fibroblasts
  • Histones/metabolism
  • Humans
  • Keratinocytes/cytology
  • Myelin Basic Protein/metabolism
  • Oncogene Proteins, Viral/physiology
  • Papillomaviridae/physiology
  • Papillomavirus E7 Proteins
  • Phenotype
  • Polyomaviridae
  • Repressor Proteins
  • Simian virus 40/immunology
  • Skin
  • Staurosporine/pharmacology

Fingerprint

Dive into the research topics of 'Staurosporine resistance accompanies DNA tumor virus-induced immortalization and is independent of the expression and activities of ERK1, ERK2, cyclin A, cyclin-dependent kinase (cdk) 2, and cdk4'. Together they form a unique fingerprint.

Cite this