Cellular ras gene activity is required for full neoplastic transformation by the large tumor antigen of SV40

L Raptis1, H L Brownell, M J Corbley

  • 1Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada. raptisl@post.queensu.ca

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|August 1, 1997
PubMed

Insights

The cellular ras (c-Ras) gene product is essential for full neoplastic transformation by the SV40 large tumor antigen (SVLT). Down-regulating c-Ras activity reduced soft agar colony formation and tumorigenicity in nude mice.

Area of Science:

  • Oncology
  • Molecular Biology
  • Virology

Background:

  • The SV40 large tumor antigen (SVLT) is known to induce neoplastic transformation in cells.
  • The role of the cellular ras (c-Ras) gene product in this process requires further elucidation.
  • Understanding the interplay between SVLT and c-Ras is crucial for cancer research.

Purpose of the Study:

  • To investigate the specific role of the c-Ras gene product in SVLT-induced neoplastic transformation.
  • To determine if c-Ras activity is necessary for all aspects of SVLT-mediated transformation.

Main Methods:

  • Murine C3H10T1/2 cells were manipulated to reduce c-Ras activity using antisense ras gene constructs or a dominant-negative ras mutant.
  • Cells were analyzed for morphological transformation, soft agar colony formation, and tumorigenicity in nude mice following SVLT expression.
  • c-Ras activity was quantified by measuring the Ras-bound GTP/GTP + GDP ratio.

Main Results:

  • SVLT-induced morphological transformation was not affected by decreased c-Ras activity.
  • However, colony formation in soft agar and tumorigenicity were significantly reduced in c-Ras-deficient cells.
  • SVLT expression led to an observable increase in cellular c-Ras activity.

Conclusions:

  • The c-Ras gene product is not essential for the initial morphological changes induced by SVLT.
  • c-Ras activity is critically required for the sustained growth and tumorigenic potential associated with SVLT transformation.
  • These findings highlight a specific requirement for c-Ras in the later stages of SVLT-driven neoplastic transformation.

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