Cadmium exposure induces expression of the HOXB8 gene in COS-7 cells.
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.
Department of Public Health and Genetic Epidemiology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Japan.
Kanako
K
Nakagawa
Myeong Jin
MJ
Lee
Naoko
N
Sasaki
Chiyo
C
Hayashi
Hisahide
H
Nishio
D000818:Animals; D019556:COS Cells; D002104:Cadmium / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000187:drug effects*; D020868:Gene Silencing / Q000187:drug effects; D005801:Genes, Homeobox / Q000187:drug effects*; D006801:Humans; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002273:Carcinogens; D012333:RNA, Messenger; D002104:Cadmium