High intracellular Zn(2+) ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells

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 o...

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Main Authors: Wong, P.F., AbuBakar, Sazaly
Format: Article
Published: 2008
Subjects:
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author Wong, P.F.
AbuBakar, Sazaly
author_facet Wong, P.F.
AbuBakar, Sazaly
author_sort Wong, P.F.
collection UM
description 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.
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spelling um.eprints-39692019-02-13T08:10:46Z http://eprints.um.edu.my/3969/ High intracellular Zn(2+) ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells Wong, P.F. AbuBakar, Sazaly R Medicine 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. 2008 Article PeerReviewed Wong, P.F. and AbuBakar, Sazaly (2008) High intracellular Zn(2+) ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells. Cellular & Molecular Biology Letters, 13 (3). pp. 375-390. ISSN 1689-1392, DOI 18311544. http://www.ncbi.nlm.nih.gov/pubmed/18311544 18311544
spellingShingle R Medicine
Wong, P.F.
AbuBakar, Sazaly
High intracellular Zn(2+) ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells
title High intracellular Zn(2+) ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells
title_full High intracellular Zn(2+) ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells
title_fullStr High intracellular Zn(2+) ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells
title_full_unstemmed High intracellular Zn(2+) ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells
title_short High intracellular Zn(2+) ions modulate the VHR, ZAP-70 and ERK activities of LNCaP prostate cancer cells
title_sort high intracellular zn 2 ions modulate the vhr zap 70 and erk activities of lncap prostate cancer cells
topic R Medicine
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AT abubakarsazaly highintracellularzn2ionsmodulatethevhrzap70anderkactivitiesoflncapprostatecancercells