Kaposi's sarcoma (KS) is the most common neoplasm in AIDS patients and is responsible for significant morbidity and mortality worldwide. There is no cure for KS, and current treatments are only able to temporarily relieve its symptoms. As part of our ongoing studies to understand the complex pathogenesis of KS, we have recently begun experiments examining Notch receptor activity in this neoplasm. Notch receptors are an evolutionarily conserved family of transmembrane receptors known to play a fundamental role in cell fate decisions including cell proliferation, differentiation and apoptosis. It is therefore not surprising that deregulated expression of Notch receptors, ligands, and/or target proteins has been associated with tumorigenesis in several cell systems. We hypothesize that deregulated Notch signaling contributes to the survival and proliferation of KS tumor cells, and Notch inactivation is a potential therapeutic strategy for KS. In this application, we propose to systematically examine Notch activity in KS tumor cells in vitro and in vivo. The studies will then be expanded to examine the biologic significance of Notch inhibition in in vitro and in vivo models of KS, including the human skin-SCID mouse model. Completion of these studies will provide new information on Notch expression and activity in KS and will determine if Notch is an appropriate target for developing new therapeutic approaches for this potentially life-threatening neoplasm.
| Curry, Christine L; Reed, Laura L; Broude, Eugenia et al. (2007) Notch inhibition in Kaposi's sarcoma tumor cells leads to mitotic catastrophe through nuclear factor-kappaB signaling. Mol Cancer Ther 6:1983-92 |
| Curry, Christine L; Reed, Laura L; Nickoloff, Brian J et al. (2006) Notch-independent regulation of Hes-1 expression by c-Jun N-terminal kinase signaling in human endothelial cells. Lab Invest 86:842-52 |
| Curry, Christine L; Reed, Laura L; Golde, Todd E et al. (2005) Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi's sarcoma tumor cells. Oncogene 24:6333-44 |
