Hypoxia promotes apoptosis of human neuroblastoma cell lines with enhanced N-myc expression.
We have examined the effect of hypoxia and nutrient depletion on the growth of human neuroblastoma cells with normal or enhanced expression of the N-myc oncogene. The combination of both conditions reduced the growth of neuroblastoma cells with normal N-myc expression. However, this effect was much more pronounced in neuroblastoma cells with enhanced N-myc expression and eventually resulted in apoptosis, presumably by the up-regulation of CD95. Our data suggest that therapeutic induction of tumor hypoxia and nutrient depletion (for example, by anti-angiogenesis) could help to improve the outcome of patients with neuroblastomas carrying the prognostically unfavourable N-myc amplification.
Rössler
J
J
Department of Pediatric Hematology, Oncology, and Endocrinology, Children's University Hospital, University of Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Schwab
M
M
Havers
W
W
Schweigerer
L
L
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D015687:Cell Hypoxia; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004274:DNA, Recombinant; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010100:Oxygen / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000032:analysis
D016895:Culture Media, Serum-Free; D004274:DNA, Recombinant; D016271:Proto-Oncogene Proteins c-myc; D019014:fas Receptor; D010100:Oxygen