Expression of a human polyomavirus oncoprotein and tumour suppressor proteins in medulloblastomas

Mol Pathol. 2001 Oct;54(5):331-7. doi: 10.1136/mp.54.5.331.

Abstract

Aims: Although the aetiology of medulloblastoma remains elusive, several lines of evidence suggest an association with the human neurotropic polyomavirus JC and its oncoprotein T antigen. The tumour forming properties of JC virus T antigen are the result, at least in part, of its ability to bind and inactivate tumour suppressor/cell cycle regulatory proteins, such as p53 and the retinoblastoma family of proteins.

Methods: To examine potential relations between these factors, immunohistochemistry was used to determine associations between the T antigen and the expression of p53 and the retinoblastoma proteins pRb, p107, and Rb2/p130 in eight medulloblastomas.

Results: Only the three medulloblastomas with T antigen expression also showed nuclear positivity with antibodies to p53. Although immunohistochemistry detected nuclear labelling for pRb in five of the cases, the three that were positive for T antigen showed the highest pRb labelling. The retinoblastoma related proteins p107 and Rb2/p130 were also immunopositive in most T antigen positive medulloblastomas. Double label immunohistochemistry also demonstrated p53 and pRb positivity in the same cells that were T antigen positive.

Conclusions: These correlations suggest that associations between T antigen and p53 and/or T antigen and pRb occur in some of these tumours. These data provide indirect evidence that JC virus, acting through T antigen, might be involved in the formation and progression of medulloblastoma.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Polyomavirus Transforming / metabolism*
  • Case-Control Studies
  • Cerebellar Neoplasms / metabolism*
  • Cerebellar Neoplasms / virology
  • Child
  • Child, Preschool
  • Female
  • Fungal Proteins*
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Infant
  • Infant, Newborn
  • JC Virus / immunology
  • Male
  • Medulloblastoma / metabolism*
  • Medulloblastoma / virology
  • Middle Aged
  • Nuclear Proteins / metabolism
  • Phosphoproteins / metabolism
  • Polymerase Chain Reaction
  • Proteins*
  • Retinoblastoma-Like Protein p107
  • Retinoblastoma-Like Protein p130
  • Serine Endopeptidases / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antigens, Polyomavirus Transforming
  • Fungal Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Proteins
  • RBL1 protein, human
  • RBL2 protein, human
  • Retinoblastoma-Like Protein p107
  • Retinoblastoma-Like Protein p130
  • Tumor Suppressor Protein p53
  • Serine Endopeptidases