Inverse correlation between expression of multidrug resistance gene and N-myc oncogene in human neuroblastomas.
Genomic amplification of N-myc is an important prognostic indicator in neuroblastoma. The tumors with amplified N-myc are initially sensitive to chemotherapy but often acquire resistance to therapy, recur, and ultimately kill the patients. We measured amplification and expression of N-myc and expression of mdr-1 in 35 surgically resected neuroblastomas, before acquisition of drug resistance and in 4 recurrent tumors resistant to chemotherapy. The mdr-1 mRNA expression was found to be inversely correlated with the N-myc expression. The mdr-1 gene expression was at a low level in advanced stage and histologically undifferentiated neuroblastomas, the same group of tumors in which N-myc expression is elevated. A significantly better prognosis was noted in those patients whose tumors had a high level of mdr-1 expression and a low level of N-myc expression. The role, if any, of increased expression of mdr-1 in the acquisition of multidrug resistance in neuroblastoma remains unclear. However, the aggressive clinical behavior associated with N-myc amplification and/or expression appears to be linked to down-regulation of mdr-1 expression.
Nakagawara
A
A
Department of Pediatric Surgery, Faculty of Medicine, Kyushu University 60, Fukuoka, Japan.
Kadomatsu
K
K
Sato
S
S
Kohno
K
K
Takano
H
H
Akazawa
K
K
Nose
Y
Y
Kuwano
M
M
D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D007223:Infant; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009857:Oncogenes; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016019:Survival Analysis
D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm