• Login
    View Item 
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    •   Home
    • UA Graduate and Undergraduate Research
    • UA Theses and Dissertations
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UA Campus RepositoryCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournal

    My Account

    LoginRegister

    About

    AboutUA Faculty PublicationsUA DissertationsUA Master's ThesesUA Honors ThesesUA PressUA YearbooksUA CatalogsUA Libraries

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    In Vitro and In Vivo Effects of Conjugated Linoleic Acid on Mammary Tumorigenesis

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    azu_etd_10164_sip1_m.pdf
    Size:
    3.977Mb
    Format:
    PDF
    Description:
    azu_etd_10164_sip1_m.pdf
    Download
    Author
    Flowers, Margaret
    Issue Date
    2008
    Keywords
    breast cancer
    conjugate linoleic acid
    ERBB2
    FASN
    HER2/neu
    PyV-mT
    Advisor
    Thompson, Patricia A.
    Committee Chair
    Thompson, Patricia A.
    
    Metadata
    Show full item record
    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    Conjugated linoleic acid (CLA) exhibits multiple biological and molecular activities that have made it the subject of considerable nutrition-related research. Numerous studies support broad acting anti-tumor effects including anti-inflammatory, anti-proliferation, and pro-apoptosis in a variety of model systems. CLA’s ability to influence multiple tumor promoting pathways, without toxicity, may prove valuable in the chemoprevention of breast cancer. The overall objective of this dissertation research was to investigate the potential of CLA in the chemoprevention of breast cancer in a subgroup of women at risk of developing estrogen receptor (ER) negative disease. Overexpression of either the ERBB2 oncogene or the epidermal growth factor receptor (EGFR) is a common event in ER negative breast cancer. To respond to this association, the stated research objective was pursued in relevant model systems. The primary hypothesis was that CLA would downregulate the ERBB2 receptor in vitro and inhibit mammary tumorigenesis in vivo. The t10c12 CLA isomer significantly reduced ERBB2 protein expression in the ERBB2 overexpressing cell line SKBr3. This was accompanied by a decrease in NFκB nuclear localization, cyclooxygenase-2 (COX2)-derived prostaglandin (PG) E2 production, increased apoptosis, and inhibition of proliferation. In contrast to the in vitro data, however 1% dietary CLA had pro-tumor effects in the PyV-mT transgenic mouse model, Mammary gland whole mounts indicated a significant loss of adipose in the CLA-treated group compared to controls that was confirmed by the downregulation of adipocyte-specific genes including PPARγ and adiponectin. CLA’s effect on the adipose was supported by decreases in fatty acid synthase at the protein and mRNA level. cDNA microarray revealed significant downregulation of cytoskeletal and adhesion-related genes in the CLA-treated group. These data suggest CLA’s combined effect on the adipose and epithelial architecture may have promoted tumor growth in this model While the large body of evidence supporting an anti-tumor effect of CLA can not be discounted, the studies herein demonstrate the complexity of its action that may not be captured in simple model systems. Reports of adverse effects of mixed isomers or the t10c12 purified isomer lend caution to supplementation that is supported by our in vivo data.
    Type
    text
    Electronic Dissertation
    Degree Name
    Ph.D.
    Degree Level
    doctoral
    Degree Program
    Nutritional Sciences
    Graduate College
    Degree Grantor
    University of Arizona
    Collections
    Dissertations

    entitlement

     
    The University of Arizona Libraries | 1510 E. University Blvd. | Tucson, AZ 85721-0055
    Tel 520-621-6442 | repository@u.library.arizona.edu
    DSpace software copyright © 2002-2017  DuraSpace
    Quick Guide | Contact Us | Send Feedback
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.