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Zinc and Metallothionein Levels and Expression of Zinc Transporters in Androgen-Independent Subline of LNCaP Cells

KENICHIRO ISHII

TAKEHISA ONISHI

YOSHIKI SUGIMURA

From the ^* Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Mitahora-higashi, Gifu, Japan; Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee; and the Department of Urology, Mie University School of Medicine, Edobashi, Tsu, Mie, Japan.

Correspondence to: Dr Kazuyuki Hirano, Laboratory of Pharmaceutics, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan (e-mail: hirano{at}gifu-pu.ac.jp).

Zinc levels in the prostate have been reported to be associated with the development and progression of malignant prostate cells. To investigate the reason why the zinc content decreases during the progression of prostate cancer to an androgen-independent state, we compared the expression levels of metallothionein and zinc transporters between androgen-responsive LNCaP cells and its androgen-independent subline, AIDL cells. AIDL cells showed lower zinc levels than LNCaP cells and comparable levels of androgen receptor expression to LNCaP cells, consistent with some clinical aspects of androgen-independent prostatic cancer. AIDL cells exhibited a lower expression of zinc transporter 1 (ZnT1) and higher expression of ZnT3 than LNCaP cells. The content of metallothionein, which is a major zinc-binding protein, was significantly lower in AIDL cells than in LNCaP cells. Furthermore, the expression of ZnT3 mRNA was decreased by incubating LNCaP cells in medium containing hormone-stripped fetal calf serum and increased by addition of synthetic androgen R1881 to the medium, whereas the intracellular zinc levels were not affected under these conditions. These findings suggest that factors such as ZnT1 and metallothioneins other than ZnT3 are associated with the low intracellular zinc content in AIDL cells.

     Key words: Hormone-refractory, metallothionein, ZnT1, ZnT3

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