Human polyomavirus BK (BKV) and neuroblastoma: mechanisms of oncogenic action and possible strategy for novel treatment.
BACKGROUND
We reported previously that nearly all human neuroblastomas analyzed contain and express genomic DNA sequences deriving from the human polyomavirus BK (BKV) [Flaegstad et al.: Cancer Res 59:1160-1163, 1999].


METHODS
Here we show that the BKV large T antigen is expressed and bound to p53 in neuroblastoma cells and that this interference compromises the tumor suppressor function of p53.


RESULTS
Treatment of neuroblastoma cells with large T antigen antisense constructs relocated active p53 to the nucleus. The relocation event was accompanied by enhanced p21(waf1/cip1) expression as well as induced apoptosis.


CONCLUSIONS
Continuous antisense oligonucleotide treatment of nude rats with human neuroblastoma xenografts resulted in a significant but incomplete reduction of tumor growth compared to rats treated with saline.
Jørgensen
G E
GE
Department of Pediatrics, Faculty of Medicine, University of Tromsø, Norway.
Johnsen
J I
JI
Ponthan
F
F
Kogner
P
P
Flaegstad
T
T
Traavik
T
T
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000032:analysis* / Q000276:immunology*; D016158:Genes, p53 / Q000276:immunology*; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics* / Q000628:therapy / Q000821:virology*; D051381:Rats; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming