Neuroblastoma: inhibition of progression (Part II). Basic science in pediatric surgery.
In neuroblastoma, amplification of the protooncogene N-myc is the most important molecular characteristic predicting a bad outcome for the patients. Despite the importance of the N-myc gene, little is known about the mechanisms regulating its expression. We found evidence that insulin-like growth factor II stimulates the growth of neuroblastoma in a paracrine fashion. Two neuroblastoma cell lines predominantly expressed IGF-II whereas two other cell lines expressed the IGF-receptor. In a receptor-positive cell line, N-myc expression was enhanced by stimulation with IGF-II. As the growth-stimulating signals of the IGF receptor are transmitted via Ras proteins, inactivation of Ras is one promising tool to prevent the induction of N-myc expression by IGF-II. Treatment of neuroblastoma cells with an inhibitor of the farnesyl-protein-transferase (FPTase) inactivated H-ras protein completely and N-ras protein by more than 50 %. Cell growth of neuroblastoma cells in serum containing medium was clearly diminished by inhibition of FPTase. The growth-promoting effect of IGF-II was reduced to exactly half the amount observed in non-inhibited cells.
Girgert
R
R
Department of Pediatric Surgery, University of Tübingen, Germany. rainer.girgert@medizin.uni-ulm.de
Wittrock
J
J
Schweizer
P
P
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000494:pharmacology*; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D017451:Receptors, Somatomedin / Q000032:analysis; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D007335:Insulin-Like Growth Factor II; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; D018631:ras Proteins