TexasScholarWorks
    • Login
    • Submit
    View Item 
    •   Repository Home
    • UT Electronic Theses and Dissertations
    • UT Electronic Theses and Dissertations
    • View Item
    • Repository Home
    • UT Electronic Theses and Dissertations
    • UT Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Characterization of metastasis regulators in human breast cancer: implications for tumor suppressor PTEN and the Rho family of small GTPases

    Thumbnail
    View/Open
    baugherp67058.pdf (2.257Mb)
    Date
    2005
    Author
    Baugher, Paige Jennette
    Share
     Facebook
     Twitter
     LinkedIn
    Metadata
    Show full item record
    Abstract
    Cancer metastasis is a multi-faceted process requiring the disregualtion of numerous signaling pathways, including those associated with cell adhesion and motility. Recent data indicates strongly that growth at a primary tumor site and growth at a metastatic site differ by the expression and/or context-dependent function of the metastasis regulator, and that a wide variety of signaling pathways are affected. PTEN (phosphatase and tensin homologue deleted on chromosome ten) then becomes an attractive candidate for a metastasis suppressor, based on its ability to negatively regulate numerous pathways involved in cell survival, cell proliferation, and cell motility. Conversely, the Rho family of small GTPases have become attractive candidates as contributors to metastasis. Rho GTPases regulate numerous signaling pathways involved in cell survival, cell proliferation and cell motility, but they function to enhance these processes instead of inhibiting them. Data presented here demonstrates the ability of PTEN to negatively regulate motility in human metastatic breast cancer cells without causing the cells to undergo apoptosis. PTEN is localized in stimulated cells away from the leading edge, which displaces it from sites of active motility signaling and prevents it from inhibiting these processes. Furthermore, ectopic PTEN expression is shown to downregulate phosphoinositol (3,4,5) triphosphate (PIP3), expression. Therefore, PTEN could be acting as a metastasis suppressor in human breast cancer. Data presented here also demonstrate the ability of the Rac subfamily of Rho GTPases to enhance metastatic properties and contribute to metastasis. Increased Rac activity was shown to correlate with increased metastatic potential in a panel of metastatic human breast cancer cell variants. When activated Rac1 or Rac3 was expressed stably in the least metastatic variant, either isoform was found to enhance adhesion, migration, and invasion in vitro, as well as contribute to pulmonary metastasis in the nude mouse model of experimental metastasis. Conversely, when dominant negative Rac1 or Rac3 was expressed in the most metastatic variant, either isoform was found to decrease adhesion, migration, and invasion in vitro, as well as block pulmonary metastasis in vivo. Therefore, Rac1 and/or Rac3 are found to act as metastasis regulators by negatively regulating metastatic human breast cancer progression.
    Department
    Institute for Cellular and Molecular Biology
    Description
    text
    URI
    http://hdl.handle.net/2152/1507
    Collections
    • UT Electronic Theses and Dissertations

    University of Texas at Austin Libraries
    • facebook
    • twitter
    • instagram
    • youtube
    • CONTACT US
    • MAPS & DIRECTIONS
    • JOB OPPORTUNITIES
    • UT Austin Home
    • Emergency Information
    • Site Policies
    • Web Accessibility Policy
    • Web Privacy Policy
    • Adobe Reader
    Subscribe to our NewsletterGive to the Libraries

    © The University of Texas at Austin

     

     

    Browse

    Entire RepositoryCommunities & CollectionsDate IssuedAuthorsTitlesSubjectsDepartmentsThis CollectionDate IssuedAuthorsTitlesSubjectsDepartments

    My Account

    Login

    Statistics

    View Usage Statistics

    Information

    About Contact Policies Getting Started Glossary Help FAQs

    University of Texas at Austin Libraries
    • facebook
    • twitter
    • instagram
    • youtube
    • CONTACT US
    • MAPS & DIRECTIONS
    • JOB OPPORTUNITIES
    • UT Austin Home
    • Emergency Information
    • Site Policies
    • Web Accessibility Policy
    • Web Privacy Policy
    • Adobe Reader
    Subscribe to our NewsletterGive to the Libraries

    © The University of Texas at Austin