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Cadmium (Cd) is a serious toxic metal, which is classified as a possible human carcinogen. We assessed the effects of Cd on the expression levels of homeobox genes, which are associated with carcinogenesis. Among 6 homeobox genes examined in this study, only HOXB8 exhibited increased mRNA expression in COS-7 cells treated with 10 microM CdCl(2). Semiquantitative reverse transcription-polymerase chain reaction analysis revealed that the HOXB8 mRNA level was increased by a maximum of 5.4-fold after 6h of Cd exposure. The levels of HOXA7, A9, C4, C9 and C10 mRNAs decreased from 0.1 to 0.3-fold. Silencing of HOXB8 mRNA expression using a siRNA increased HOXC9 and C10 mRNA expression levels by 6.6- and 1.9-fold, respectively. These results suggest that HOXB8 upregulation is associated with suppression of HOXC9 and C10, and that decreased expression of HOXC9 and C10 after Cd exposure is partly due to HOXB8 induction. In conclusion, Cd disrupts the HOX network. Comprehensive analyses of all the HOX gene expression levels in the presence of Cd may afford clues toward understanding Cd-induced carcinogenesis and teratogenesis.

Exposure of cells to cadmium (Cd) is known to stimulate the expression of various types of genes. These changes in gene expression are presumed to be related to the cellular response to Cd toxicity. To better understand the mechanisms related to Cd toxicity, suppression subtractive hybridization was carried out on COS-7 cells (African green monkey kidney cells) and the gene expression induced by Cd exposure was investigated. Heat shock protein (hsp) 10, 40, 60, 70, 89alpha and metallothionein II (MTII) mRNAs were found to be induced by Cd. This is the first report to describe the Cd-inducibility of hsp10, 40 and 89alpha mRNAs. Semi-quantitative reverse-transcription polymerase chain reaction showed the diverse expression patterns of these genes, depending on Cd concentration and exposure time. A marked elevation of hsp70 mRNA and induction of mRNA for the co-chaperone, hsp40, were detected. A relatively low level of hsp10 and hsp60 mRNAs was induced, with only a 2-fold increase within 24 h. Hsp89alpha mRNA was induced shortly after Cd exposure. These various induction patterns suggest that hsps play different roles in the cell against Cd toxicity.