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Enumeration of the simian virus 40 early region elements necessary for human cell transformation

William C Hahn1, Scott K Dessain, Mary W Brooks

  • 1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.

Molecular and Cellular Biology
|March 9, 2002
PubMed

Insights

Simian virus 40 (SV40) early region proteins, along with hTERT and H-ras, transform human cells by disrupting key tumor suppressor pathways. Small t antigen (ST) is crucial for full transformation, enabling proliferation and survival.

Area of Science:

  • Molecular Biology
  • Oncology
  • Virology

Background:

  • Cancer develops from accumulated genetic mutations leading to uncontrolled cell growth.
  • Understanding specific mutation combinations driving human tumor growth is crucial.
  • DNA tumor viruses provide insights into cell transformation mechanisms.

Purpose of the Study:

  • To elucidate the role of the simian virus 40 (SV40) early region (ER) in human cell tumorigenic transformation.
  • To identify the specific SV40 antigens and intracellular pathways involved in transformation.
  • To define the minimal elements of SV40 ER required for generating tumorigenic human cells.

Main Methods:

  • Coexpression of SV40 early region (ER), human telomerase reverse transcriptase (hTERT), and oncogenic H-ras in normal human cells.
  • Analysis of SV40 large T antigen (LT) and small t antigen (ST) functions in disrupting intracellular pathways.
  • Assessment of cell proliferation, anchorage-independent growth, and nutrient deprivation resistance.

Main Results:

  • SV40 ER, hTERT, and H-ras coexpression induce tumorigenic transformation in human cells.
  • SV40 LT disables retinoblastoma (pRB) and p53 tumor suppressor pathways.
  • SV40 ST is essential for complete transformation, perturbing protein phosphatase 2A, stimulating proliferation, enabling anchorage-independent growth, and conferring resistance to nutrient deprivation.

Conclusions:

  • The SV40 early region contains essential elements for human cell transformation.
  • Disruption of pRB, p53, and protein phosphatase 2A pathways by SV40 LT and ST is critical for tumorigenesis.
  • These findings delineate a set of intracellular pathways whose combined disruption generates tumorigenic human cells.

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