Cadmium causes increases of N-myc and multidrug-resistance gene mRNA in neuroblastoma cells.
Since cadmium exposure results in neuropathological alterations in central nervous system, we investigated the effects of cadmium on the gene expression of neuroblastoma (GOTO) cells. We observed an increase in mRNA levels of heat-shock protein (hsp) 70, hsp 90, hsp 32 and metallothionein after treatment of GOTO cells with cadmium, although the time courses of the changes of individual mRNA of the heat-shock proteins and metallothionein were somewhat different from each other. An accumulation of N-myc and multidrug-resistance gene (MDR1) mRNA was detected in the presence of cadmium. This is contrary to the previous report, in which an inverse correlation between the expression of MDR1 gene and N-myc oncogene in human neuroblastoma had been described. However, the increase of N-myc and MDR1 mRNA in the present study is not likely due to the loss of regulatory mechanism of these genes by cytotoxic effects of cadmium, because active protective mechanisms such as heat-shock proteins and metallothionein could be induced under these conditions.
Murakami
T
T
Department of Biochemistry, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Ohmori
H
H
Katoh
T
T
Abe
T
T
Higashi
K
K
D002104:Cadmium / Q000009:adverse effects*; D004351:Drug Resistance / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D005796:Genes / Q000187:drug effects*; D016259:Genes, myc / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D008668:Metallothionein / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D002104:Cadmium; D008668:Metallothionein