Control of Transformation and Invasiveness of Breast Cancer Cells by Estrogen Regulation of Proteinase Inhibitor 9

摘要

Thrombosis, or the abnormal clotting of the blood, is the leading cause of death in breast cancer patients. Thrombus formation is triggered factor Vlla from circulating blood encounters tissue factor (TF) on the surface of a cell, including many breast cancer cells and tumor-associated cells. It is important, therefore, to increase our understanding of the mechanisms by which TF activates the clotting cascade in breast cancer. The blood protein, antithrombin (AT), has long been thought to be the most important natural anticoagulant that targets steps of the clotting cascade downstream from TF:Vlla, but more recent work has suggested that AT can also inactivate factor Vlla bound to TF. Goals of this project included determining if AT can efficiently inhibit TF:Vlla complexes and if resulting factor Vlla-antithrombin (VIla-AT) complexes can be detected in blood. The project was successful in determining that the TF:Vlla complex can efficiently be inactivated by AT, and furthermore was successful in quantifying Vlla-AT levels in blood.