N-myc oncogene amplification is correlated to trace metal concentrations in neuroblastoma cultured cells

N-myc oncogene amplification is a powerful predictor of aggressive behavior of neuroblastoma (NB), the most common solid tumor of the early childhood. Since N-myc overexpression - subsequent to amplification - determines a ph enotype of invasiveness and metastatic spreading, it is assumed that N-myc amplified neuroblasts synthesize zinc metalloenzymes leading to tumor invas ion and formation of metastases. In order to test a possible relation betwe en N-myc oncogene amplification and trace metal contents in human NE cells, Fe, Cu and Zn concentrations have been measured by nuclear microprobe anal ysis in three human neuroblastoma cell lines with various degrees of N-myc amplification. Elemental determinations show uniform distribution of trace metals within the cells, but variations of intracellular trace metal concen trations with respect to the degree of N-myc amplification are highly depen dent on the nature of the element. Zinc concentration is higher in both N-m yc amplified cell lines (IMR-32 and IGR-N-91) than in the non-amplified cel ls (SK-N-SH). In contrast, intracellular iron content is particularly low i n N-myc amplified cell lines. Moreover, copper concentrations showed an inc rease with the degree of N-myc amplification. These results indicate that a relationship exists between intracellular trace metals and N-myc oncogene amplification. They further suggest that trace metals very probably play a determinant role in mechanisms of the neuroblastoma invasiveness. (C) 2000 Elsevier Science B.V. All rights reserved.