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 p...

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Bibliographic Details
Published in:Cancer letters 2003-10, Vol.200 (2), p.187-195
Main Authors: Hasumi, Masaru, Suzuki, Kazuhiro, Matsui, Hiroshi, Koike, Hidekazu, Ito, Kazuto, Yamanaka, Hidetoshi
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Cadmium
Cadmium - pharmacology
Cancer therapies
Carcinogens
Carrier Proteins - genetics
Carrier Proteins - metabolism
Cell Division
Gene expression
Gene Expression Regulation
Humans
Male
Medical sciences
Metallothionein
Metallothionein - genetics
Metallothionein - metabolism
Metals
Molecular weight
Pharmacology. Drug treatments
Prostate cancer
Prostatic Neoplasms - genetics
Protein expression
Proteins
RNA, Messenger - analysis
Studies
Tumor Cells, Cultured
Tumors
Ultrasonic imaging
Zinc
Zinc - metabolism
Zinc - pharmacology
Zinc transporter
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Summary: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.
ISSN:0304-3835
1872-7980
DOI:10.1016/S0304-3835(03)00441-5