Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress

H. C. Whitaker; D. Patel; W. J. Howat; A. Y. Warren; J. D. Kay; T. Sangan; J. C. Marioni; J. Mitchell; S. Aldridge; H. J. Luxton; C. Massie; A. G. Lynch; D. E. Neal

doi:10.1038/bjc.2013.396

Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress

H. C. Whitaker^*, D. Patel, W. J. Howat, A. Y. Warren, J. D. Kay, T. Sangan, J. C. Marioni, J. Mitchell, S. Aldridge, H. J. Luxton, C. Massie, A. G. Lynch, D. E. Neal

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Objective:We have previously identified peroxiredoxin-3 (PRDX-3) as a cell-surface protein that is androgen regulated in the LNCaP prostate cancer (PCa) cell line. PRDX-3 is a member of the peroxiredoxin family that are responsible for neutralising reactive oxygen species.Experimental design:PRDX-3 expression was examined in tissue from 32 patients using immunohistochemistry. Subcellular distribution was determined using confocal microscopy. PRDX-3 expression was determined in antiandrogen-resistant cell lines by western blotting and quantitative RT-PCR. The pathways of PRDX-3 overexpression and knockdown on apoptosis and response to oxidative stress were investigated using protein arrays. Results: PRDX-3 is upregulated in a number of endocrine-regulated tumours; in particular in PCa and prostatic intraepithelial neoplasia. Although the majority of PRDX-3 is localised to the mitochondria, we have confirmed that PRDX-3 at the cell membrane is androgen regulated. In antiandrogen-resistant LNCaP cell lines, PRDX-3 is upregulated at the protein but not RNA level. Resistant cells also possess an upregulation of the tricarboxylic acid (TCA) pathway and resistance to H₂O ₂-induced apoptosis through a failure to activate pro-Apoptotic pathways. Knockdown of PRDX-3 restored H₂O₂ sensitivity. Conclusion: Our results suggest that PRDX-3 has an essential role in regulating oxidation-induced apoptosis in antiandrogen-resistant cells. PRDX-3 may have potential as a therapeutic target in castrate-independent PCa.

Original language	English
Pages (from-to)	983-993
Number of pages	11
Journal	British Journal of Cancer
Volume	109
Issue number	4
DOIs	https://doi.org/10.1038/bjc.2013.396
Publication status	Published - 20 Aug 2013

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10.1038/bjc.2013.396

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Whitaker, H. C., Patel, D., Howat, W. J., Warren, A. Y., Kay, J. D., Sangan, T., Marioni, J. C., Mitchell, J., Aldridge, S., Luxton, H. J., Massie, C., Lynch, A. G., & Neal, D. E. (2013). Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress. British Journal of Cancer, 109(4), 983-993. https://doi.org/10.1038/bjc.2013.396

@article{4614a1a555bc4542bde3b2ce419e38e1,

title = "Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress",

abstract = "Objective:We have previously identified peroxiredoxin-3 (PRDX-3) as a cell-surface protein that is androgen regulated in the LNCaP prostate cancer (PCa) cell line. PRDX-3 is a member of the peroxiredoxin family that are responsible for neutralising reactive oxygen species.Experimental design:PRDX-3 expression was examined in tissue from 32 patients using immunohistochemistry. Subcellular distribution was determined using confocal microscopy. PRDX-3 expression was determined in antiandrogen-resistant cell lines by western blotting and quantitative RT-PCR. The pathways of PRDX-3 overexpression and knockdown on apoptosis and response to oxidative stress were investigated using protein arrays. Results: PRDX-3 is upregulated in a number of endocrine-regulated tumours; in particular in PCa and prostatic intraepithelial neoplasia. Although the majority of PRDX-3 is localised to the mitochondria, we have confirmed that PRDX-3 at the cell membrane is androgen regulated. In antiandrogen-resistant LNCaP cell lines, PRDX-3 is upregulated at the protein but not RNA level. Resistant cells also possess an upregulation of the tricarboxylic acid (TCA) pathway and resistance to H2O 2-induced apoptosis through a failure to activate pro-Apoptotic pathways. Knockdown of PRDX-3 restored H2O2 sensitivity. Conclusion: Our results suggest that PRDX-3 has an essential role in regulating oxidation-induced apoptosis in antiandrogen-resistant cells. PRDX-3 may have potential as a therapeutic target in castrate-independent PCa.",

author = "Whitaker, {H. C.} and D. Patel and Howat, {W. J.} and Warren, {A. Y.} and Kay, {J. D.} and T. Sangan and Marioni, {J. C.} and J. Mitchell and S. Aldridge and Luxton, {H. J.} and C. Massie and Lynch, {A. G.} and Neal, {D. E.}",

year = "2013",

month = aug,

day = "20",

doi = "10.1038/bjc.2013.396",

language = "English",

volume = "109",

pages = "983--993",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature publishing group",

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Whitaker, HC, Patel, D, Howat, WJ, Warren, AY, Kay, JD, Sangan, T, Marioni, JC, Mitchell, J, Aldridge, S, Luxton, HJ, Massie, C, Lynch, AG & Neal, DE 2013, 'Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress', British Journal of Cancer, vol. 109, no. 4, pp. 983-993. https://doi.org/10.1038/bjc.2013.396

TY - JOUR

T1 - Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress

AU - Whitaker, H. C.

AU - Patel, D.

AU - Howat, W. J.

AU - Warren, A. Y.

AU - Kay, J. D.

AU - Sangan, T.

AU - Marioni, J. C.

AU - Mitchell, J.

AU - Aldridge, S.

AU - Luxton, H. J.

AU - Massie, C.

AU - Lynch, A. G.

AU - Neal, D. E.

PY - 2013/8/20

Y1 - 2013/8/20

N2 - Objective:We have previously identified peroxiredoxin-3 (PRDX-3) as a cell-surface protein that is androgen regulated in the LNCaP prostate cancer (PCa) cell line. PRDX-3 is a member of the peroxiredoxin family that are responsible for neutralising reactive oxygen species.Experimental design:PRDX-3 expression was examined in tissue from 32 patients using immunohistochemistry. Subcellular distribution was determined using confocal microscopy. PRDX-3 expression was determined in antiandrogen-resistant cell lines by western blotting and quantitative RT-PCR. The pathways of PRDX-3 overexpression and knockdown on apoptosis and response to oxidative stress were investigated using protein arrays. Results: PRDX-3 is upregulated in a number of endocrine-regulated tumours; in particular in PCa and prostatic intraepithelial neoplasia. Although the majority of PRDX-3 is localised to the mitochondria, we have confirmed that PRDX-3 at the cell membrane is androgen regulated. In antiandrogen-resistant LNCaP cell lines, PRDX-3 is upregulated at the protein but not RNA level. Resistant cells also possess an upregulation of the tricarboxylic acid (TCA) pathway and resistance to H2O 2-induced apoptosis through a failure to activate pro-Apoptotic pathways. Knockdown of PRDX-3 restored H2O2 sensitivity. Conclusion: Our results suggest that PRDX-3 has an essential role in regulating oxidation-induced apoptosis in antiandrogen-resistant cells. PRDX-3 may have potential as a therapeutic target in castrate-independent PCa.

AB - Objective:We have previously identified peroxiredoxin-3 (PRDX-3) as a cell-surface protein that is androgen regulated in the LNCaP prostate cancer (PCa) cell line. PRDX-3 is a member of the peroxiredoxin family that are responsible for neutralising reactive oxygen species.Experimental design:PRDX-3 expression was examined in tissue from 32 patients using immunohistochemistry. Subcellular distribution was determined using confocal microscopy. PRDX-3 expression was determined in antiandrogen-resistant cell lines by western blotting and quantitative RT-PCR. The pathways of PRDX-3 overexpression and knockdown on apoptosis and response to oxidative stress were investigated using protein arrays. Results: PRDX-3 is upregulated in a number of endocrine-regulated tumours; in particular in PCa and prostatic intraepithelial neoplasia. Although the majority of PRDX-3 is localised to the mitochondria, we have confirmed that PRDX-3 at the cell membrane is androgen regulated. In antiandrogen-resistant LNCaP cell lines, PRDX-3 is upregulated at the protein but not RNA level. Resistant cells also possess an upregulation of the tricarboxylic acid (TCA) pathway and resistance to H2O 2-induced apoptosis through a failure to activate pro-Apoptotic pathways. Knockdown of PRDX-3 restored H2O2 sensitivity. Conclusion: Our results suggest that PRDX-3 has an essential role in regulating oxidation-induced apoptosis in antiandrogen-resistant cells. PRDX-3 may have potential as a therapeutic target in castrate-independent PCa.

UR - http://www.scopus.com/inward/record.url?scp=84883144775&partnerID=8YFLogxK

U2 - 10.1038/bjc.2013.396

DO - 10.1038/bjc.2013.396

M3 - Article

AN - SCOPUS:84883144775

SN - 0007-0920

VL - 109

SP - 983

EP - 993

JO - British Journal of Cancer

JF - British Journal of Cancer

IS - 4

ER -

Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress

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