Regulation of metallothionein and zinc transporter expression in human prostate cancer cells and tissues.
Prostate glands contain heavy metals such as zinc and cadmium, and epidemiological studies showed that both metals were associated with prostate cancer development. To understand the heavy metal metabolism in prostate glands, we investigated the regulation of metallothionein (MT), metal-responsive promoter element-binding transcription factor (MTF) and zinc transporter (ZnT) in human prostate cells and tissues. Growth of human prostate cancer cells, LNCaP and PC-3 cells, was suppressed by zinc or cadmium treatment in a dose-dependent manner. LNCaP cells expressed MT-1A, 1X and 2A mRNA, and PC-3 cells expressed MT-1X and 2A mRNA. Zinc or cadmium treatment up-regulated MTs, MTF-1 and ZnT-1 gene expression levels in both cell lines. In PC-3 cells, ZnT-1 protein was detected, and was up-regulated by the metal treatment. Human prostate cancer tissues expressed significantly lower levels of ZnT-1 gene in comparison with hyperplastic tissues. We demonstrated the ZnT-1 expression in human prostate for the first time. The present study showed that heavy metal-metabolizing proteins were involved in human prostate homeostasis, and that the metal metabolizing system might be different in malignant tissues.
Department of Urology, Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Masaru
M
Hasumi
Kazuhiro
K
Suzuki
Hiroshi
H
Matsui
Hidekazu
H
Koike
Kazuto
K
Ito
Hidetoshi
H
Yamanaka
D002104:Cadmium / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
D002352:Carrier Proteins; D012333:RNA, Messenger; C407523:metallothionein isoform 1; C017800:zinc-binding protein; D002104:Cadmium; D008668:Metallothionein; D015032:Zinc