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Title page for ETD etd-08222008-132323


Type of Document Dissertation
Author Fang, Wei Bin
Author's Email Address wei.b.fang@vanderbilt.edu
URN etd-08222008-132323
Title The Role of EphA2 RTK in Breast Cancer Cell Malignancy and Tumor Angiogenesis
Degree PhD
Department Cancer Biology
Advisory Committee
Advisor Name Title
Al Reynolds Committee Chair
Ann Richmond Committee Member
Jin Chen Committee Member
Steve Hanks Committee Member
Keywords
  • Receptor Tyrosine Kinase
  • Breast Cancer
  • EphA2
  • Neovascularization -- Regulation
  • Protein-tyrosine kinase -- Receptors
Date of Defense 2008-08-19
Availability unrestricted
Abstract
The EphA2 receptor belongs to the recently cloned Eph family of receptor tyrosine kinase (RTK). High levels of EphA2 RTK have been detected in 60-90% of human breast cancer specimens, both in breast cancer cells and in tumor vascular endothelial cells. However, the mechanisms by which EphA2 promotes breast cancer malignancy are not completely clear. In my dissertation work, I first investigated the effect of EphA2 overexpression on tumor cells. I found that increased EphA2 expression in normal epithelial cells contributes to destabilization of cell-cell adhesion, an early step towards tumor cell malignancy; whereas high levels of EphA2 expression in tumor cells increase tumor cell motility and lung metastasis. In addition to regulating tumor cell malignancy, EphA2 also promotes tumor angiogenesis. In order to dissect EphA2 signaling in vascular endothelial cells, I mapped phosphorylated tyrosine residues on the EphA2 receptor, identified interacting proteins that bind to these sites, and tested the effects of a series of phosphorylation-defective EphA2 mutants on angiogenesis. These studies established a critical role for tyrosine phosphorylation of EphA2 in tumor angiogenesis. Taken together, my thesis work demonstrated that EphA2 regulates tumor progression by promoting both tumor cell malignancy and tumor angiogenesis.
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