ANTISENSE OLIGONUCLEOTIDES AS INHIBITORS OF BREAST & TUMOR-INDUCED ANGIOGENESIS

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Tumor progression requires the formation of new capillary blood vessels. It is very likely that anti-angiogenesis agents will be effective in preventing the recurrence of metastasis of many types of tumors. We are investigating the role of the ETS1 proto-oncogene in angiogenesis. We have confirmed that expression of this gene in human umbilical vein endothelial cells (HUVECs) is induced by treatment with phorbol myristic acid. We wish to confirm the role of this gene in angiogenesis by examining the effect of antisense oligonucleotides based on the ets sequence on the behavior of endothelial cells. Properties to be monitored include cell proliferation, differentiation, chemotaxis and invasiveness. We also wish to identify other genes involved in angiogenesis by using the differential display technique to isolate cDNAs corresponding to mRNAs that are expressed differentially between endothelial cells treated and not treated with angiogenic agents.