The Effect of eIF4E Antisense RNA Expression on Prostate Tumor Angiogenesis and Growth

Abstract

Some mRNA with complex 5' regions that are more efficiently translated in the presence of high levels of the translation initiation factor eIF4E are particularly important to the initiation and progression of prostate cancer, such as vascular enothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2), and c-myc. The purpose of our study was to investigate the ability of an eIF4E antisense RNA approach to regulate the expression of VEGF and FGF-2, and thus tumor angiogenesis, and to better define the interactions between eIF4E and c-myc or p53 (which we suspect may be regulated by eIF4E as well) in prostate cancer. Each of 6 prostate tumor cell lines stably transduced with a retrovirus-mediated eIF4E anti sense (4EAS) make less VEGF, FGF-2, and are significantly less able to recruit vascular cells or to stimulate either proliferation or differentiation into capillary-like structures than the parental cells. Suppression of eIF4E did not appear to influence the isoforms of FGF-2 expressed, but did appear to alter the relative abundance of particular VEGF isoforms. Animals injected with 4EAS transduced cells did not develop tumors compared with animals injected with parental cells, and 4EAS- seeded sponges were infiltrated with significantly fewer new blood vessels than sponges seeded with parental cells.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 1999
Accession Number
ADA383175

Entities

People

  • Briana J. Williams

Organizations

  • LSU Health Sciences Center New Orleans

Tags

DTIC Thesaurus Topics

  • Angiogenesis
  • Antisense Elements (Genetics)
  • Biochemistry
  • Blood Vessels
  • Cell Line
  • Cells
  • Chemistry
  • Culture Media
  • Endothelial Cells
  • Gene Therapy
  • Health Services
  • Microvessels
  • Molecular Biology
  • Neoplasms
  • Prostate
  • Prostate Cancer
  • Proteins

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and genetic basis of cancer.