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    ROLE OF BTG2 IN THE ANTIOXIDANT RESPONSE IN HUMAN BREAST EPITHELIAL CELLS.

    Cover for ROLE OF BTG2 IN THE ANTIOXIDANT RESPONSE IN HUMAN BREAST EPITHELIAL CELLS.
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    View/Open: Karve_georgetown_0076D_11871.pdf (4.4MB) Bookview

    Creator
    Karve, Tejaswita Mohan
    Advisor
    Rosen, Eliot M
    Abstract
    BTG2, a member of antiproliferative gene family BTG/TOB, has been implicated in cell cycle regulation, normal development and tumor suppression. However, the underlying mechanism(s) by which BTG2 regulates these processes is still unclear. Previously, it has been shown that BTG2 expression is either completely lost or down-regulated in human breast cancers. Herein, I found that BTG2 protects human mammary epithelial cells from oxidative stress due to hydrogen peroxide (H2O2) and other oxidants, namely, nickel acetate and paraquat. Further, I showed that BTG2-mediated protection against oxidative stress in human breast epithelial cells is BRCA1 independent but requires the antioxidant-response transcription factor NFE2L2. The cytoprotective role of BTG2 is partly mediated by up-regulating the activity of key antioxidant enzymes including catalase, superoxide dismutase (SOD) 1, SOD2, and glutathione peroxidase, which are also NFE2L2-depedent. Additionally, I showed that BTG2 increases the transcriptional activity of the antioxidant transcriptional factor, NFE2L2. Furthermore, our immunoprecipitation results indicate that BTG2 is a binding partner of NFE2L2; with this physical interaction being facilitated by Box B, a short highly conserved amino acid motif characteristic of BTG2/TOB family proteins, but not by Box A or Box C of BTG2 protein. I also show that Box B of BTG2 is required for the antioxidant stimulation effects mediated by BTG2 in response to H2O2 induced oxidative stress. Finally, I show that BTG2 is present at the AREs of NFE2L2 responsive genes (i.e., NQO1 and HO-1). These findings suggest a novel role for BTG2, as a co-activator of NFE2L2, in up-regulating cellular antioxidant defenses in response to oxidative stress in human breast cells.
    Description
    Ph.D.
    Permanent Link
    http://hdl.handle.net/10822/557515
    Date Published
    2012
    Subject
    Antioxidant response; Breast cancer; BTG2; Co-activator; NFE2L2-ARE signaling; Oxidative stress; Molecular biology; Biochemistry; Cytology; Molecular biology; Biochemistry; Cellular biology;
    Type
    thesis
    Publisher
    Georgetown University
    Extent
    152 leaves
    Collections
    • Graduate Theses and Dissertations - Biochemistry and Molecular & Cellular Biology
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    Georgetown University Seal
    ©2009 - 2023 Georgetown University Library
    37th & O Streets NW
    Washington DC 20057-1174
    202.687.7385
    digitalscholarship@georgetown.edu
    Accessibility