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Increased Skin Papilloma Formation in Mice Lacking Glutathione Transferase GSTP

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Increased Skin Papilloma Formation in Mice Lacking Glutathione Transferase GSTP. / Henderson, Colin J.; Ritchie, Kenneth J.; McLaren, Aileen; Chakravarty, Probir; Wolf, C. Roland (Lead / Corresponding author).

In: Cancer Research, Vol. 71, No. 22, 15.11.2011, p. 7048-7060.

Research output: Contribution to journalArticle

Harvard

Henderson, CJ, Ritchie, KJ, McLaren, A, Chakravarty, P & Wolf, CR 2011, 'Increased Skin Papilloma Formation in Mice Lacking Glutathione Transferase GSTP' Cancer Research, vol 71, no. 22, pp. 7048-7060.

APA

Henderson, C. J., Ritchie, K. J., McLaren, A., Chakravarty, P., & Wolf, C. R. (2011). Increased Skin Papilloma Formation in Mice Lacking Glutathione Transferase GSTP. Cancer Research, 71(22), 7048-7060doi: 10.1158/0008-5472.CAN-11-0882

Vancouver

Henderson CJ, Ritchie KJ, McLaren A, Chakravarty P, Wolf CR. Increased Skin Papilloma Formation in Mice Lacking Glutathione Transferase GSTP. Cancer Research. 2011 Nov 15;71(22):7048-7060.

Author

Henderson, Colin J.; Ritchie, Kenneth J.; McLaren, Aileen; Chakravarty, Probir; Wolf, C. Roland (Lead / Corresponding author) / Increased Skin Papilloma Formation in Mice Lacking Glutathione Transferase GSTP.

In: Cancer Research, Vol. 71, No. 22, 15.11.2011, p. 7048-7060.

Research output: Contribution to journalArticle

Bibtex - Download

@article{ab6bb22b9d384ed4974af8a8e48e11af,
title = "Increased Skin Papilloma Formation in Mice Lacking Glutathione Transferase GSTP",
author = "Henderson, {Colin J.} and Ritchie, {Kenneth J.} and Aileen McLaren and Probir Chakravarty and Wolf, {C. Roland}",
year = "2011",
volume = "71",
number = "22",
pages = "7048--7060",
journal = "Cancer Research",
issn = "0008-5472",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Increased Skin Papilloma Formation in Mice Lacking Glutathione Transferase GSTP

A1 - Henderson,Colin J.

A1 - Ritchie,Kenneth J.

A1 - McLaren,Aileen

A1 - Chakravarty,Probir

A1 - Wolf,C. Roland

AU - Henderson,Colin J.

AU - Ritchie,Kenneth J.

AU - McLaren,Aileen

AU - Chakravarty,Probir

AU - Wolf,C. Roland

PY - 2011/11/15

Y1 - 2011/11/15

N2 - <p>The glutathione S-transferase GSTP is overexpressed in many human cancers and chemotherapy-resistant cancer cells, where there is evidence that GSTP may have additional functions beyond its known catalytic role. On the basis of evidence that Gstp-deficient mice have a comparatively higher susceptibility to skin carcinogenesis, we investigated whether this phenotype reflected an alteration in carcinogen detoxification or not. For this study, Gstp(-/-) mice were interbred with Tg.AC mice that harbor initiating H-ras mutations in the skin. Gstp(-/-)/Tg.AC mice exposed to the proinflammatory phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) exhibited higher tumor incidence and multiplicity with a significant thickening of skin after treatment, illustrating hyperproliferative growth. Unexpectedly, we observed no difference in cellular proliferation or apoptosis or in markers of oxidative stress, although higher levels of the inflammatory marker nitrotyrosine were found in Gstp(-/-)/Tg.AC mice. Instead, gene set enrichment analysis of microarray expression data obtained from skin revealed a more proapoptotic and proinflammatory environment shortly after TPA treatment. Within 4 weeks of TPA treatment, Gstp(-/-)/Tg.AC mice displayed altered lipid/sterol metabolism and Wnt signaling along with aberrant processes of cytoskeletal control and epidermal morphogenesis at both early and late times. In extending the evidence that GSTP has a vital role in normal homeostatic control and cancer prevention, they also strongly encourage the emerging concept that GSTP is a major determinant of the proinflammatory character of the tumor microenvironment. This study shows that the GSTP plays a major role in carcinogenesis distinct from its role in detoxification and provides evidence that the enzyme is a key determinant of the proinflammatory tumor environment. Cancer Res; 71(22); 7048-60. (C)2011 AACR.</p>

AB - <p>The glutathione S-transferase GSTP is overexpressed in many human cancers and chemotherapy-resistant cancer cells, where there is evidence that GSTP may have additional functions beyond its known catalytic role. On the basis of evidence that Gstp-deficient mice have a comparatively higher susceptibility to skin carcinogenesis, we investigated whether this phenotype reflected an alteration in carcinogen detoxification or not. For this study, Gstp(-/-) mice were interbred with Tg.AC mice that harbor initiating H-ras mutations in the skin. Gstp(-/-)/Tg.AC mice exposed to the proinflammatory phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) exhibited higher tumor incidence and multiplicity with a significant thickening of skin after treatment, illustrating hyperproliferative growth. Unexpectedly, we observed no difference in cellular proliferation or apoptosis or in markers of oxidative stress, although higher levels of the inflammatory marker nitrotyrosine were found in Gstp(-/-)/Tg.AC mice. Instead, gene set enrichment analysis of microarray expression data obtained from skin revealed a more proapoptotic and proinflammatory environment shortly after TPA treatment. Within 4 weeks of TPA treatment, Gstp(-/-)/Tg.AC mice displayed altered lipid/sterol metabolism and Wnt signaling along with aberrant processes of cytoskeletal control and epidermal morphogenesis at both early and late times. In extending the evidence that GSTP has a vital role in normal homeostatic control and cancer prevention, they also strongly encourage the emerging concept that GSTP is a major determinant of the proinflammatory character of the tumor microenvironment. This study shows that the GSTP plays a major role in carcinogenesis distinct from its role in detoxification and provides evidence that the enzyme is a key determinant of the proinflammatory tumor environment. Cancer Res; 71(22); 7048-60. (C)2011 AACR.</p>

KW - SET ENRICHMENT ANALYSIS

KW - GERMINAL CENTER KINASE

KW - TG.AC TRANSGENIC MICE

KW - S-TRANSFERASE

KW - PROMOTER METHYLATION

KW - TUMOR-DEVELOPMENT

KW - MOUSE-MODEL

KW - PI

KW - GENE

KW - EXPRESSION

U2 - 10.1158/0008-5472.CAN-11-0882

DO - 10.1158/0008-5472.CAN-11-0882

M1 - Article

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 22

VL - 71

SP - 7048

EP - 7060

ER -

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