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

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87 Scopus citations

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
State	Published - Aug 20 2013
Externally published	Yes

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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{03946938465846a08818c2caebe6443d,

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",

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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 - Artículo

C2 - 23880827

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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