High intracellular Zn(2+) ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells
Document Type
Article
Publication Date
1-1-2008
Abstract
Malignant prostate tissues have markedly reduced zinc (Zn(2+)) contents in comparison to non-malignant tissues. In this study, we restored a high intracellular Zn(2+) level to LNCaP prostate cancer cells by culturing the cells in a growth medium supplemented with a supraphysiological concentration of Zn(2+) (10 mu g/ml) over 5 weeks. The intracellular Zn(2+) level increased in the Zn(2+)-treated cells, and there was a marked increase in the presence of zincosomes, a Zn(2+)-specific intracellular organelle. The proliferation rate of the Zn(2+)-treated cells was markedly reduced. There was also a significant increase (36.6 +/- 6.4) in the total tyrosine phosphorylated proteins. Vaccinia H1-related (VHR) phosphatase, zeta chain-associated protein-70 (ZAP-70) kinase and phosphorylated extracellular signal-regulated protein kinase 1 and 2 (p-ERK 1 and 2) were also present in higher abundance. Treatment with TPEN, which chelates Zn(2+), reduced the abundance of VHR phosphatase and ZAP-70 kinase, but increased the abundance of p-ERK 1. However, the TPEN treatment restored the Zn(2+)-treated LNCaP cell proliferation to a rate comparable to that of the non Zn(2+)-treated cells. These results highlight the importance of a high intracellular Zn(2+) content and the VHR/ZAP-70-associated pathways in the modulation of LNCaP prostate cancer cell growth.
Keywords
Animals Cell Line, Tumor Cell Proliferation Chelating Agents/metabolism Culture Media/chemistry Dual Specificity Phosphatase 3/*metabolism Ethylenediamines/metabolism Extracellular Signal-Regulated MAP Kinases/*metabolism Humans Male Prostatic Neoplasms/*metabolism Protein Tyrosine Phosphatases/metabolism Protein-Tyrosine Kinases/metabolism ZAP-70 Protein-Tyrosine Kinase/*metabolism Zinc/*metabolism
Divisions
fac_med
Publication Title
Cellular & Molecular Biology Letters
Volume
13
Issue
3
Additional Information
Wong, Pooi-Fong Abubakar, Sazaly eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Poland 2008/03/04 09:00 Cell Mol Biol Lett. 2008;13(3):375-90. Epub 2008 Feb 29.