Activation of androgen response element by cadmium: a potential mechanism for a carcinogenic effect of cadmium in the prostate.
Cadmium is a transition metal that has been widely used in industry. Epidemiological and animal studies have demonstrated a carcinogenic effect of cadmium on the prostate. Although it has been established that androgen is required for this cancer-inducing process, it is not clear how cadmium interacts with androgen. In this study, the carcinogenic mechanism of cadmium was explored with a focus on interaction of androgen and cadmium at the gene transcription level. An androgen response luciferase reporter was used for analysis of the cadmium activity in the transient transfection assay. Human prostate epithelial cells (LNCap) and liver cells (HepG2) were transfected by the reporter. The result showed that cadmium was able to activate the reporter in the absence of androgen, and that this activation was dependent on the presence of androgen receptor. Cadmium could enhance the androgen response when both androgen and cadmium were applied together to the reporter-transfected cells. Activation of the reporter by cadmium was not associated with cell proliferation or interleukin 6 (IL-6) production, which was proposed to be involved in cadmium-induced carcinogenesis in other experimental systems. Cadmium exhibited a weak ability to induce AP-1. The results demonstrate that cadmium has an androgen-like activity in prostate epithelial cells, and this activity implies a new mechanism for the carcinogenic effect of cadmium in the prostate.
Ye
J
J
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Wang
S
S
Barger
M
M
Castranova
V
V
Shi
X
X
D000728:Androgens / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002104:Cadmium / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D004347:Drug Interactions; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000187:drug effects / Q000502:physiology*; D020218:Response Elements / Q000187:drug effects* / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D000728:Androgens; D002273:Carcinogens; D011944:Receptors, Androgen; D002104:Cadmium; D008156:Luciferases