Abstract #1033

Angiogenin, is a 14.2 kD polypeptide member of the RNase A superfamily of enzymes with potent angiogenic activity. Angiogenin binds to endothelial cells and induces proliferation, cell migration, and invasion. Nuclear accumulation of angiogenin is essential for its angiogenic activity. In breast cancer, increased angiogenin expression has been associated with the transition from normal to invasive breast carcinoma and to ER expression. We have previously reported a pro-angiogenic action of estradiol and anti-angiogenic activity of tamoxifen in breast cancer by regulation of VEGF secretion and generation of endostatin. In this paper we investigated if estradiol and/or tamoxifen affected angiogenin. We show that estradiol increased and tamoxifen decreased angiogenin secretion of human breast cancer cells in culture. In vivo, in solid human breast cancers in nude mice, tamoxifen therapy decreased angiogenin extracellularly, sampled using microdialysis. Moreover, estradiol-induced angiogenin derived from cancer cells significantly increased human endothelial cell (HUVEC) proliferation. Adding tamoxifen to the estradiol treatment as well as an antibody against angiogenin, reversed this increase. Additionally, exposure of tamoxifen to HUVEC in culture significantly decreased the endogenous secretion of angiogenin as well as the translocation of angiogenin to the nucleus. We conclude that angiogenin expression is estrogen-regulated in human breast cancer cells. In addition, decreased secretion of angiogenin by cancer and endothelial cells, and a restrained nuclear accumulation of angiogenin, may suggest novel anti-angiogenic mechanisms of tamoxifen. This may be a target for anti-estrogen therapeutic options in the future.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1033.

Thirty-first San Antonio Breast Cancer Symposium Dec 10-14, 2008; San Antonio, TX