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• W2327258219 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCProstate cancer is the most frequently diagnosed malignancy in men and the second leading cause of cancer related deaths in the United States of America. Advanced stage prostate cancer is associated with poor prognosis since no effective therapies are available when the disease has progressed into a hormone refractory state. This grim prognosis indicates the need for novel approaches to the treatment of advanced stage prostate cancer. One such therapeutic strategy is anti-angiogenic therapy, which interferes with the blood supply of the tumor instead of targeting tumor cells directly. Here we focus on the role of Rap1, a small GTPase homologous to Ras, and its upstream activator, Epac, a guanine nucleotide exchange factor for Rap1, in angiogenesis. In previous studies, we showed that treatment of primary human microvascular endothelial cells (HMVEC) with 8 CPT-2Me-cAMP (8-CPT), a specific agonist of Epac, or introduction of constitutively active Rap1 into these cells blocked VEGF-mediated chemotaxis and inhibited angiogenesis in mice. To test the efficacy of Epac/Rap1 activation in a tumor model, we injected an Epac agonist, 8-CPT, in a PC-3 human prostate tumor xenograft model. Surprisingly, although 8-CPT did not alter tumor growth in PC-3 cells, the drug significantly reduced tumor size in PC-3 cells expressing constitutively active Rap1. Tumor analysis showed an increase in HIF-1α,VEGF and CD31 immunostaining in Rap1-expressing tumors, and a significant decrease in their levels upon treatment of the mice with the Epac agonist 8-CPT. Similar reductions in VEGF and Glut-1 mRNA levels and HIF-1α protein were observed in Rap1-PC-3 cells following 8-CPT treatment when cells were cultured under hypoxic conditions. On the basis of these results, we propose that expression of Rap1 in the PC-3 human prostate tumor cell line promotes hypoxic induction of angiogenesis and increases the susceptibility of the cells to anti-angiogenic agents.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2379." @default.
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• W2327258219 date "2010-04-15" @default.
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• W2327258219 title "Abstract 2379: Rap1 regulates angiogenesis in prostate tumors" @default.
• W2327258219 doi "https://doi.org/10.1158/1538-7445.am10-2379" @default.
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