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Extinction of Tumor Antigen Expression by SF2/ASF in JCV-Transformed Cells

Elena Uleri1, Sarah Beltrami, Jennifer Gordon

  • 1Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA, USA.

Genes & Cancer
|December 31, 2011
PubMed

Insights

The splicing factor SF2/ASF suppresses JC virus (JCV) oncogene expression, inhibiting tumor growth. Downregulation of SF2/ASF promotes proliferation in JCV-transformed cells, revealing its tumor suppressor role.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Human neurotropic polyomavirus JC (JCV) is linked to neural-origin tumors, including medulloblastomas and glioblastomas.
  • JCV's oncogenic activity stems from its early gene products, large T and small t antigens.
  • The splicing factor SF2/ASF was previously shown to negatively regulate JCV gene transcription and splicing in glial cells.

Purpose of the Study:

  • To investigate the role of SF2/ASF in JCV-mediated cellular transformation and tumor development.
  • To determine if SF2/ASF expression affects the oncogenic activity of JCV tumor antigens.
  • To identify the functional domain of SF2/ASF responsible for its tumor suppressor activity.

Main Methods:

  • Assessing SF2/ASF's effect on large T antigen expression in JCV-transformed tumor cell lines.
  • Evaluating the impact of SF2/ASF expression levels on tumor cell proliferation and transformation.
  • Performing mapping analysis to identify the minimal peptide domain of SF2/ASF involved in JCV promoter silencing and tumor suppression.

Main Results:

  • SF2/ASF directly suppresses large T antigen expression in JCV-transformed tumor cells, thereby inhibiting their transforming capacity.
  • Down-regulation of SF2/ASF in these cells leads to increased tumor cell growth and proliferation.
  • Amino acid residues 76 to 100 of SF2/ASF were identified as the minimal functional domain for suppressing tumor cell growth.

Conclusions:

  • SF2/ASF acts as a tumor suppressor by inhibiting JCV's oncogenic activity.
  • SF2/ASF plays a critical role in regulating JCV-mediated cellular transformation.
  • These findings offer new insights into the pathogenic mechanisms of JCV-induced tumors and potential therapeutic targets.
Keywords:
JC virusSF2/ASFtranscriptiontumor antigen

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