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In vivo regulation of human glutathione transferase GSTP by chemopreventive agents.

Authors :
Henderson CJ
McLaren AW
Wolf CR
Source :
Cancer research [Cancer Res] 2014 Aug 15; Vol. 74 (16), pp. 4378-87. Date of Electronic Publication: 2014 Jun 16.
Publication Year :
2014

Abstract

Relatively little progress has been made in determining the in vivo regulation of glutathione S-transferase P (GSTP), particularly the human enzyme hGSTP1, despite being identified as a significant factor in carcinogenesis and development of drug resistance in tumor cell lines. Here, we report the characterization of a transgenic reporter mouse that reveals how hGSTP1 is regulated in vivo by chemopreventive agents. Basal expression was found in crypts and villi of the small and large intestine, bronchiolar epithelial cells, the epidermis and hair follicles, gall bladder epithelium, choroid plexus, and biliary epithelium. Expression was induced in different tissues by the antioxidant chemopreventive agents ethoxyquin and butylated hydroxyanisole. However, genetic deletion of the Nrf2 transcription factor, which directs central genetic programs of detoxification and protection against oxidative stress, increased rather than attenuated GSTP1 expression. In vitro investigations with mouse embryonic fibroblasts revealed factors, in addition to Nrf2, that control the expression of GSTP1, offering further insights into regulation. The new reporter mouse described here provides a useful tool to gain deeper insights into the mechanisms of action of chemopreventive compounds and other environmental agents.<br /> (©2014 American Association for Cancer Research.)

Details

Language :
English
ISSN :
1538-7445
Volume :
74
Issue :
16
Database :
MEDLINE
Journal :
Cancer research
Publication Type :
Academic Journal
Accession number :
24934809
Full Text :
https://doi.org/10.1158/0008-5472.CAN-14-0792