In vivo regulation of human glutathione transferase GSTP by chemopreventive agents

Colin J. Henderson, Aileen W. McLaren, C. Roland Wolf (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    19 Citations (Scopus)

    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 (EQ) and butylated hydroxyanisole (BHA). However, genetic deletion of the transcription factor Nrf2, 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 factor(s) 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.
    Original languageEnglish
    Pages (from-to)4378-4387
    Number of pages10
    JournalCancer Research
    Volume74
    Issue number16
    Early online date16 Jun 2014
    DOIs
    Publication statusPublished - 15 Aug 2014

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