TY - DATA T1 - In Vivo Bioluminescence Imaging of Furin Activity in Breast Cancer Cells Using Bioluminogenic Substrates PY - 2009/08/19 AU - Anca Dragulescu-Andrasi AU - Gaolin Liang AU - Jianghong Rao UR - https://acs.figshare.com/articles/journal_contribution/In_Vivo_Bioluminescence_Imaging_of_Furin_Activity_in_Breast_Cancer_Cells_Using_Bioluminogenic_Substrates/2834422 DO - 10.1021/bc9002508.s001 L4 - https://ndownloader.figshare.com/files/4532116 KW - proprotein convertases family endoprotease KW - bioluminescent emission KW - Breast Cancer Cells KW - probe furin function KW - furin activity KW - Vivo Bioluminescence Imaging KW - furin activation N2 - Furin, a proprotein convertases family endoprotease, processes numerous physiological substrates and is overexpressed in cancer and inflammatory conditions. Noninvasive imaging of furin activity will offer a valuable tool to probe furin function over the course of tumor growth and migration in the same animals in real time and directly assess the inhibition efficacy of drugs in vivo. Here, we report successful bioluminescence imaging of furin activity in xenografted MBA-MB-468 breast cancer tumors in mice with bioluminogenic probes. The probes are conjugates of furin substrate, a consensus amino acid motif R-X-K/R-R (X, any amino acid), with the firefly luciferase substrate d-aminoluciferin. In the presence of the luciferase reporter, the probes are unable to produce bioluminescent emission without furin activation. Blocking experiments with a furin inhibitor and control experiments with a scrambled probe showed that the bioluminescence emission in the presence of firefly luciferase is furin-dependent and specific. After furin activation, a 30-fold increase in the bioluminescent emission was observed in vitro, and on average, a 7−8-fold contrast between the probe and control was seen in the same tumor xenografts in mice. Direct imaging of furin activity may facilitate the study of furin function in tumorigenicity and the discovery of new drugs for furin-targeted cancer therapy. ER -