Expression of a human polyomavirus oncoprotein and tumour suppressor proteins in medulloblastomas.
OBJECTIVE
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.
Del Valle
L
L
The Center for NeuroVirology and Cancer Biology, Temple University, Philadelphia, PA 19122, USA.
Baehring
J
J
Lorenzana
C
C
Giordano
A
A
Khalili
K
K
Croul
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D016022:Case-Control Studies; D002528:Cerebellar Neoplasms / Q000378:metabolism* / Q000821:virology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005656:Fungal Proteins; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007577:JC Virus / Q000276:immunology; D008297:Male; D008527:Medulloblastoma / Q000378:metabolism* / Q000821:virology; D008875:Middle Aged; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011506:Proteins; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D012697:Serine Endopeptidases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000952:Antigens, Polyomavirus Transforming; D005656:Fungal Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C493844:RBL1 protein, human; C493837:RBL2 protein, human; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D016159:Tumor Suppressor Protein p53; D012697:Serine Endopeptidases