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Critical role for SV40 small-t antigen in human cell transformation

J Yu1, A Boyapati, K Rundell

  • 1Department of Microbiology-Immunology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.

Virology
|March 9, 2002
PubMed

Insights

Simian virus 40 (SV40) small-t antigen is crucial for transforming human fibroblasts, even with large-T antigen. This viral protein is essential for most human cell transformations, unlike ras oncogenes.

Area of Science:

  • Virology
  • Oncology
  • Cell Biology

Background:

  • Simian virus 40 (SV40) is increasingly implicated in human malignancies.
  • Understanding SV40's transforming capabilities is vital for cancer research.
  • Previous studies highlighted the role of SV40 large-T (LT) antigen in transformation.

Purpose of the Study:

  • To define the role of SV40 small-t (ST) antigen in LT-driven transformation of human cells.
  • To investigate whether c-Ha-ras (EJ-ras) can substitute for ST in human cell transformation.
  • To determine the necessity of telomerase for SV40-mediated transformation and immortalization.

Main Methods:

  • Transformation assays using primary human fibroblasts.
  • Introduction of SV40 LT antigen, ST antigen, and/or EJ-ras oncogene.
  • Development and characterization of immortalized human mesothelial cell lines.
  • Assessment of cellular immortalization and transformation phenotypes.

Main Results:

  • SV40 ST antigen is essential for LT-driven transformation of primary human fibroblasts.
  • The oncogene EJ-ras cannot substitute for ST in this process.
  • Telomerase is not essential for initial transformation but is required for immortalization of transformed cells.
  • SV40 LT and telomerase can immortalize human mesothelial cells, which then require ST for transformation.

Conclusions:

  • SV40 ST antigen is a critical determinant for the transformation of most human cell types by SV40.
  • The viral ST antigen plays a unique and indispensable role in human oncogenesis mediated by SV40.
  • Ras oncogenes cannot fulfill the function of ST in SV40-mediated transformation of human cells.

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