Functional Significance of Transcriptional Regulation by VEGF Receptor Tyrosine Kinases

Abstract

The relationship between angiogenesis and breast cancer tumorigenesis has been well established. VEGF is a leading candidate for a molecular mediator of tumor angiogenesis. VEGF is expressed by tumor cells in vitro and in vivo; blocking VEGF signaling arrests tumor angiogenesis and tumor growth in vivo. Based on these findings, it is clear that understanding the molecular mechanisms that drive the endothelial responses to VEGF will improve our understanding of tumor angiogenesis. Several of the signaling molecules that associate with the activated VEGF receptors influence pathways involved in transcriptional regulation in the nucleus. We hypothesize that the angiogenic effects of VEGF signaling are attributable, at least in part, to the activation of transcriptional regulation of gene expression. Thus, the goal of the study undertaken is to identify genes that are regulated by VEGF RTK activation and to determine the functional significance of these genes in tumor angiogenesis. We have completed two screens, a cDNA Representational Difference Analysis screen and another using the Gene Discovery Array filters. We further explored the role of C3G and CD9 in VEGF-mediated angiogenesis, but ruled them out. We are currently exploring the role of SOCS2, a negative regulatory protein, in the VEGF angiogenic pathway.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 1999
Accession Number
ADB258877

Entities

People

  • Adrianne L. Wong

Organizations

  • Duke University Hospital

Tags

DTIC Thesaurus Topics

  • Angiogenesis
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Movement
  • Cells
  • Chemistry
  • Endothelial Cells
  • Gene Expression
  • Government Procurement
  • Governments
  • Maryland
  • Molecules
  • Neoplasms
  • Regulations
  • Standards
  • Universities

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology (Cancer Research).