Title page for etd-0623113-200356


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URN etd-0623113-200356
Author Yu-chen Tseng
Author's Email Address No Public.
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Department Institute of Biomedical Sciences
Year 2012
Semester 2
Degree Master
Type of Document
Language zh-TW.Big5 Chinese
Title Functional and Receptor-interacting Studies of Hepatoma-derived growth factor (HDGF)
Date of Defense 2013-07-18
Page Count 71
Keyword
  • Hepatoma
  • HDGF
  • Akt pathway
  • Epithelial–mesenchymal transition
  • Abstract Hepatoma-derived growth factor (HDGF) is a nuclear protein with both mitogenic and angiogenic activity that trigger tumor progression in various types of cancer including hepatocellular carcinoma. In this study, we characterized the different domains of HDGF using functional assays in tumor stimulation in human SK-Hep1 cells. Proliferation analysis revealed the exogenous C140 domain of HDGF protein remarkably increased the cell growth of SK-Hep1 cells but the PWWP domain slightly enhanced the cell growth when compared with PBS control group. In addition, adding exogenous C140 domain protein also stimulated colony formation and invasion of SK-Hep1 cells, indicating the functional domain of HDGF was located in C140 domain. Next, we further validated that the mutation from serine to alanine on Ser103 phosphorylation site of HDGF by site-directed mutagenesis attenuated HDGF-stimulating cell proliferation, colony formation and invasion but the mutation form serine to glutamine did not influence the stimulatory effect of HDGF. Finally, western blotting shown that PWWP domain and S103A mutant HDGF protein were not triggered PI3K/AKT signaling pathway and downstream EMT relative gene expression including E-cadherin and Vimentin. In conclusion, these results demonstrated that C140 domain was a major functional fragment in HDGF-regulated several cellular functions in SK-Hep1 hepatoma cells, and more important phosphorylation site Ser103 mutation to alanine could eliminate the effect. The present study provides evidence that targeting C140 domain of HDGF may well be a novel strategy for the treatment of hepatoma.
    Advisory Committee
  • Kuang-hung Cheng - chair
  • Ching-Mei Hsu - co-chair
  • Ming-Hong Tai - advisor
  • Files
  • etd-0623113-200356.pdf
  • Indicate in-campus at 99 year and off-campus access at 99 year.
    Date of Submission 2013-08-12

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