The Effect of eIF4E Antisense RNA Expression on Prostate Tumor Angiogenesis and Growth
Final rept. 1 Sep 1998-28 Feb 2001
LOUISIANA STATE UNIV IN SHREVEPORT HEALTH SCIENCE CENTER
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We set out to investigate the role of the translation initiation factor elF4E in prostate cancer angiogenesis and to determine if suppression of elF4E could have clinical benefit. This is highly relevant to both early and late stages of prostate cancer, for tumor angiogenesis is critical to primary tumor growth, as well as metastasis. We found elevated elF4E levels in a significant number of prostate tumors where it cd-localized with both increased vascular endothelial growth factor VEGF and vessel density. We set up cell line models and saw that prostate cancer cells overexpressing elF4E had higher levels of secreted VEGF and grew faster than control cells when injected into mice, while prostate cancer cells expressing an elF4E anti-sense RNA and thus with lower elF4E levels, had depressed VEGF levels and did not grow in the mouse model. Unlike other cell types, however, in prostate cells, elF4E expression was not associated with any change in the expression pattern of isoforms of FGF-2 or VEGF. In addition, elF4E expression did not appear to be correlated with p53 status, however, we are continuing to investigate whether levels of p53 protein may be in part regulated at the level of translation.
- Medicine and Medical Research