Human polyomavirus BK (BKV) and neuroblastoma: mechanisms of oncogenic action and possible strategy for novel treatment

Autor: G E, Jørgensen, J I, Johnsen, F, Ponthan, P, Kogner, T, Flaegstad, T, Traavik
Rok vydání: 2000
Předmět:
Zdroj: Medical and pediatric oncology. 35(6)
ISSN: 0098-1532
Popis: 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].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.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.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.
Databáze: OpenAIRE