Survivin mediates prostate cell protection by HIF-1α against zinc toxicity

Young Joo Yun, Shan Hua Li, Young Suk Cho, Jong-Wan Park, Yang Suk Chun

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13 Citations (Scopus)

Abstract

BACKGROUND. The prostate contains extremely high concentrations of zinc, but survives and grows without apparent injury. This begs the question as to how prostate cells avoid the toxic effects of zinc. In a previous study, the authors found that; HIF-1α is expressed concomitantly with the accumulation of zinc in the epithelial cells of normal rat prostates, the zinc ion stabilizes HIF-1α in prostate cells, and that HIF-1α protects prostate cells from zinc toxicity. In the present study, the authors addressed the mechanism responsible for the protective effect of HIF-1α in a high zinc environment. METHODS. Immunofluorescent staining, immunoblotting, reverse transcription-polymerase chain reaction, reporter assay, and cell cycle analysis. RESULTS. Survivin was induced by ZnCl2 in a HIF-1 dependent manner in both DU-145 and PNT2 prostate cells. Furthermore, HIF-1 induced survivin expression at the transcriptional level and the induction of survivin was abolished by HIF-1α knock-down. In addition, HIF-1-dependent survivin overexpression promoted prostrate cell survival and prevented cell arrest in the presence of high zinc concentrations, and si-survivin transfected cells under zinc rich conditions contained markedly higher levels of cleaved caspase-9 and PARP than si-con transfected cells. Finally, survivin expression patterns well matched rat prostate proliferation statuses. CONCLUSION. Under zinc rich conditions, prostate epithelial cells HIF-1-dependently express survivin, which promotes prostate cell proliferation, and prevents apoptosis and cell cycle arrest. Accordingly, the HIF-1α-survivin pathway appears to facilitate prostate cell survival and growth in zinc rich environments, and this pathway could be a therapeutic target for the treatment of prostate hyperplasia.

Original languageEnglish
Pages (from-to)1179-1188
Number of pages10
JournalProstate
Volume70
Issue number11
DOIs
StatePublished - 1 Aug 2010

Fingerprint

Cytoprotection
Zinc
Prostate
Cell Survival
Epithelial Cells
Caspase 9
Poisons
Cell Cycle Checkpoints
Immunoblotting
Reverse Transcription
Hyperplasia
Cell Cycle
Cell Proliferation
Ions
Apoptosis
Staining and Labeling

Keywords

  • Apoptosis
  • Cell cycle
  • HIF-1α
  • Prostate
  • Survivin
  • Zinc

Cite this

Yun, Young Joo ; Li, Shan Hua ; Cho, Young Suk ; Park, Jong-Wan ; Chun, Yang Suk. / Survivin mediates prostate cell protection by HIF-1α against zinc toxicity. In: Prostate. 2010 ; Vol. 70, No. 11. pp. 1179-1188.
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abstract = "BACKGROUND. The prostate contains extremely high concentrations of zinc, but survives and grows without apparent injury. This begs the question as to how prostate cells avoid the toxic effects of zinc. In a previous study, the authors found that; HIF-1α is expressed concomitantly with the accumulation of zinc in the epithelial cells of normal rat prostates, the zinc ion stabilizes HIF-1α in prostate cells, and that HIF-1α protects prostate cells from zinc toxicity. In the present study, the authors addressed the mechanism responsible for the protective effect of HIF-1α in a high zinc environment. METHODS. Immunofluorescent staining, immunoblotting, reverse transcription-polymerase chain reaction, reporter assay, and cell cycle analysis. RESULTS. Survivin was induced by ZnCl2 in a HIF-1 dependent manner in both DU-145 and PNT2 prostate cells. Furthermore, HIF-1 induced survivin expression at the transcriptional level and the induction of survivin was abolished by HIF-1α knock-down. In addition, HIF-1-dependent survivin overexpression promoted prostrate cell survival and prevented cell arrest in the presence of high zinc concentrations, and si-survivin transfected cells under zinc rich conditions contained markedly higher levels of cleaved caspase-9 and PARP than si-con transfected cells. Finally, survivin expression patterns well matched rat prostate proliferation statuses. CONCLUSION. Under zinc rich conditions, prostate epithelial cells HIF-1-dependently express survivin, which promotes prostate cell proliferation, and prevents apoptosis and cell cycle arrest. Accordingly, the HIF-1α-survivin pathway appears to facilitate prostate cell survival and growth in zinc rich environments, and this pathway could be a therapeutic target for the treatment of prostate hyperplasia.",
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Survivin mediates prostate cell protection by HIF-1α against zinc toxicity. / Yun, Young Joo; Li, Shan Hua; Cho, Young Suk; Park, Jong-Wan; Chun, Yang Suk.

In: Prostate, Vol. 70, No. 11, 01.08.2010, p. 1179-1188.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Survivin mediates prostate cell protection by HIF-1α against zinc toxicity

AU - Yun, Young Joo

AU - Li, Shan Hua

AU - Cho, Young Suk

AU - Park, Jong-Wan

AU - Chun, Yang Suk

PY - 2010/8/1

Y1 - 2010/8/1

N2 - BACKGROUND. The prostate contains extremely high concentrations of zinc, but survives and grows without apparent injury. This begs the question as to how prostate cells avoid the toxic effects of zinc. In a previous study, the authors found that; HIF-1α is expressed concomitantly with the accumulation of zinc in the epithelial cells of normal rat prostates, the zinc ion stabilizes HIF-1α in prostate cells, and that HIF-1α protects prostate cells from zinc toxicity. In the present study, the authors addressed the mechanism responsible for the protective effect of HIF-1α in a high zinc environment. METHODS. Immunofluorescent staining, immunoblotting, reverse transcription-polymerase chain reaction, reporter assay, and cell cycle analysis. RESULTS. Survivin was induced by ZnCl2 in a HIF-1 dependent manner in both DU-145 and PNT2 prostate cells. Furthermore, HIF-1 induced survivin expression at the transcriptional level and the induction of survivin was abolished by HIF-1α knock-down. In addition, HIF-1-dependent survivin overexpression promoted prostrate cell survival and prevented cell arrest in the presence of high zinc concentrations, and si-survivin transfected cells under zinc rich conditions contained markedly higher levels of cleaved caspase-9 and PARP than si-con transfected cells. Finally, survivin expression patterns well matched rat prostate proliferation statuses. CONCLUSION. Under zinc rich conditions, prostate epithelial cells HIF-1-dependently express survivin, which promotes prostate cell proliferation, and prevents apoptosis and cell cycle arrest. Accordingly, the HIF-1α-survivin pathway appears to facilitate prostate cell survival and growth in zinc rich environments, and this pathway could be a therapeutic target for the treatment of prostate hyperplasia.

AB - BACKGROUND. The prostate contains extremely high concentrations of zinc, but survives and grows without apparent injury. This begs the question as to how prostate cells avoid the toxic effects of zinc. In a previous study, the authors found that; HIF-1α is expressed concomitantly with the accumulation of zinc in the epithelial cells of normal rat prostates, the zinc ion stabilizes HIF-1α in prostate cells, and that HIF-1α protects prostate cells from zinc toxicity. In the present study, the authors addressed the mechanism responsible for the protective effect of HIF-1α in a high zinc environment. METHODS. Immunofluorescent staining, immunoblotting, reverse transcription-polymerase chain reaction, reporter assay, and cell cycle analysis. RESULTS. Survivin was induced by ZnCl2 in a HIF-1 dependent manner in both DU-145 and PNT2 prostate cells. Furthermore, HIF-1 induced survivin expression at the transcriptional level and the induction of survivin was abolished by HIF-1α knock-down. In addition, HIF-1-dependent survivin overexpression promoted prostrate cell survival and prevented cell arrest in the presence of high zinc concentrations, and si-survivin transfected cells under zinc rich conditions contained markedly higher levels of cleaved caspase-9 and PARP than si-con transfected cells. Finally, survivin expression patterns well matched rat prostate proliferation statuses. CONCLUSION. Under zinc rich conditions, prostate epithelial cells HIF-1-dependently express survivin, which promotes prostate cell proliferation, and prevents apoptosis and cell cycle arrest. Accordingly, the HIF-1α-survivin pathway appears to facilitate prostate cell survival and growth in zinc rich environments, and this pathway could be a therapeutic target for the treatment of prostate hyperplasia.

KW - Apoptosis

KW - Cell cycle

KW - HIF-1α

KW - Prostate

KW - Survivin

KW - Zinc

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U2 - 10.1002/pros.21152

DO - 10.1002/pros.21152

M3 - Article

VL - 70

SP - 1179

EP - 1188

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 11

ER -