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 anal yzed contain and express genomic DNA sequences deriving from the human poly omavirus BK (BKV) [Flaegstad et al.: Cancer Res 59:1160-1163, 1999]. Proced ure. Here we show that the BKV large T antigen is expressed and bound to p5 3 in neuroblastoma cells and that this interference compromises the tumor s uppressor function of p53. Results. Treatment of neuroblastoma cells with l arge T antigen antisense constructs relocated active p53 to the nucleus. Th e relocation event was accompanied by enhanced p21(waf1/cip1) expression as well as induced apoptosis. Conclusions. Continous antisense oligonucleotid e treatment of nude rats with human neuroblastoma xenografts resulted in a significant but incomplete reduction of tumor growth compared to rats treat ed with saline. (C) 2000 Wiley-Liss. Inc.