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High intracellular Zn2+ ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells

Abstract

Malignant prostate tissues have markedly reduced zinc (Zn2+) contents in comparison to non-malignant tissues. In this study, we restored a high intracellular Zn2+ level to LNCaP prostate cancer cells by culturing the cells in a growth medium supplemented with a supraphysiological concentration of Zn2+ (10 μg/ml) over 5 weeks. The intracellular Zn2+ level increased in the Zn2+-treated cells, and there was a marked increase in the presence of zincosomes, a Zn2+-specific intracellular organelle. The proliferation rate of the Zn2+-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 Zn2+, reduced the abundance of VHR phosphatase and ZAP-70 kinase, but increased the abundance of p-ERK 1. However, the TPEN treatment restored the Zn2+-treated LNCaP cell proliferation to a rate comparable to that of the non Zn2+-treated cells. These results highlight the importance of a high intracellular Zn2+ content and the VHR/ZAP-70-associated pathways in the modulation of LNCaP prostate cancer cell growth.

Abbreviations

ERK:

extracellular signal-regulated protein kinase

KAP:

kinase-associated phosphatase

PTK:

protein tyrosine kinase

PTP:

protein tyrosine phosphatase

PTP1B:

protein tyrosine phosphatase 1B

PTP1C/SHP-1:

protein tyrosine phosphatase 1C

TPEN:

N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine

VHR:

vaccinia H1-related

ZAP-70:

zeta chain-associated protein-70

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Correspondence to Sazaly Abubakar.

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Wong, PF., Abubakar, S. High intracellular Zn2+ ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells. Cell Mol Biol Lett 13, 375–390 (2008). https://doi.org/10.2478/s11658-008-0009-6

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  • DOI: https://doi.org/10.2478/s11658-008-0009-6

Keywords

  • Cancer
  • ERK
  • Prostate
  • VHR
  • ZAP-70
  • Zn2+