Angiogenesis and Cancer Prevention by Selenium
Annual rept. 15 May 2000-14 May 2001
AMC CANCER RESEARCH CENTER DENVER CO
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Our overall aim is to understand the role of inhibition of angiogenesis in breast cancer prevention by selenium Se. We have during the current funding period focused on following up on our discovery of a specific selenium metabolite inhibitory effect on vascular endothelial expression of matrix metalloproteinases and have extended that specificity to the inhibition of vascular endothelial growth factor VEGF by breast cancer epithelial cells. Our paper describing these findings received cover story honor in Mol. Carcinogenesis, 2000. We have also developed methodologies for evaluating anti-angiogenic attributes pro-angiogenic factors, mitogenesis, apoptosis, capillary differentiation etc of Se and validated with other agents and these activities resulted in 4 publications and reviews. Because endothelial matrix degradation, mitogenesis and survival are essential for angiogenesis response and because VEGF is crucial for stimulating angiogenesis, these observations provide plausible mechanisms to account for how methylselenol metabolite pool regulates angiogenic switch during chemoprevention of mammary and other cancers. For the next year, we will pursue the metabolite-specific effects on endothelial mitogenesis and cell cycle regulation and apoptosis and the role of JNK, p38MAPK, ERKs and PI3K signaling in angiogenesis regulation by methylselenium.
- Medicine and Medical Research