The Effect of eIF4E Antisense RNA Expression on Prostate Tumor Angiogenesis and Growth
Annual rept. 1 Sep 1998-31 Aug 1999
LOUISIANA STATE UNIV MEDICAL CENTER SHREVEPORT
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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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