Title page for etd-0624115-165153


[Back to Results | New Search]

URN etd-0624115-165153
Author Chun-Yu Chen
Author's Email Address No Public.
Statistics This thesis had been viewed 5574 times. Download 8 times.
Department Biological Sciences
Year 2014
Semester 2
Degree Master
Type of Document
Language zh-TW.Big5 Chinese
Title The role of betulinic acid in modulation of membrane microdomains and TGF-β signaling.
Date of Defense 2015-07-21
Page Count 64
Keyword
  • cholesterol
  • TGF-beta
  • caveolae
  • lipid-raft
  • Betulinic acid
  • Abstract Betulinic acid (BetA) is a phytochemical triterpenoid acid from bark extracts and is cytotoxic to cancer cells and tumors. The specific subcellular receptors that are bound or deactivated by BetA have not been extensively investigated or identified. The goal of this study is to investigate the effect of BetA in transforming growth factor β (TGF-β) signaling. TGF-β is a key modulator in regulating cell proliferation and migration, it also involved in the process of cancer development and progression. TGF-β regulates tumor cell proliferation and invasion through a variety of Smad-dependent and -independent pathways. In most of cells, TGF-β receptors were located predominantly in lipid raft/caveolae microdomains, determined using sucrose density gradient ultracentrifugation and Western blot. BetA induces translocation of TGF-β receptors from lipid raft/caveolae to non-caveolae microdomains without changing total level of TGF-β receptors. Distribution of TGF-β receptors between lipid raft/caveolae- and clathrin-mediated endocytosis has been found to regulate TGF-β responsiveness. Most notably, BetA-induced TGF-β receptors translocation is rapid and correlate with the TGF-β-induced signaling. Here, we provide for the first the time evidence that BetA enhanced TGF-β signaling is associated with translocation of TGF-β receptors out of lipid raft/caveolae microdomains and a dramatic increase in the ability of TGF-β to stimulate Smad2 phosphorylation. Moreover, BetA-induced redistribution of TGF-β receptors also enhances TGF-β -induced PAI-1 reporter gene activation and growth inhibition in Mv1Lu cells. These results implicated that anticancer activities of BetA may be due, in part to the enhancing of TGF-β receptor signaling in non-caveolae microdomains in plasma membrane.
    Advisory Committee
  • Yaw-Bin Huang - chair
  • Jenq-Lin Yang - co-chair
  • Chen, Chun-Lin - advisor
  • Files
  • etd-0624115-165153.pdf
  • Indicate in-campus at 5 year and off-campus access at 5 year.
    Date of Submission 2015-07-24

    [Back to Results | New Search]


    Browse | Search All Available ETDs

    If you have more questions or technical problems, please contact eThesys