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    Identification of ESE-1 as a novel molecular target of chemopreventive agents for colon cancer prevention

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    Date
    2019
    Author
    Lee, Jihye
    Advisor
    Lee, Seong-Ho
    DRUM DOI
    https://doi.org/10.13016/am0k-pg27
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    Abstract
    Epithelial specific ETS-1 (ESE-1) is one of the E26 transformation-specific transcription factor superfamily and could be considerable interest as a possible target for regulating diverse types of human cancer. Despite its clinical importance, the reported biological role of ESE-1 on cancer development and progression are still controversial and its underlying mechanisms of tumorigenesis remains unclear. The objectives of this dissertation are to elucidate the role of ESE-1 in tumorigenesis. With the evidence in cancer phenotypes, the underlying mechanisms of ESE-1 in colon cancer was also investigated. ESE-1 knockout mice increased azoxymethane (AOM) -induced and dextran sulfate sodium (DSS)-promoted formation of aberrant crypt foci (ACF) compared to wild type mice. Overexpression of ESE-1 suppressed anchorage-independent growth and migration/invasion in human colon cancer cells and while knockdown of ESE-1 reversed anti-cancer activity. Full length ESE-1 was abundantly found in the nucleus, and internal deletion of nuclear localization sequence 2 (NLS2) decreased the amount of nuclear ESE-1. Three lysine residues (318KKK320) in the NLS2 were critical for nuclear localization of ESE-1 and mediates tumor suppressive activity of ESE-1 through reduced beta-catenin transcriptional activity. We identified two anti-cancer natural compounds, epigallocatechin-3-gallate (EGCG) and patchouli alcohol as ESE-1 inducers. Both EGCG and patchouli alcohol increased expression of ESE-1 protein and mRNA in human colon cancer cells. Patchouli alcohol showed reduced the number of tumors and tumor load in Apcmin/+ colon cancer animal model although protein expression level of ESE-1 did not show significant difference. These findings suggest a potential use of ESE-1 as a novel and potential molecular target of natural anti-cancer phytochemicals for colon cancer prevention.
    URI
    http://hdl.handle.net/1903/25446
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    • Nutrition & Food Science Theses and Dissertations
    • UMD Theses and Dissertations

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    DRUM is brought to you by the University of Maryland Libraries
    University of Maryland, College Park, MD 20742-7011 (301)314-1328.
    Please send us your comments.
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