Abstract A73: Understanding specificity in Notch receptor signaling

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 23_Supplement; p. A73
• Main Authors: Bell, Alisa, Okamura, Heidi, Keane, David, Perino, Samantha, Lorusso, Jeanine, Gyuris, Jeno, O'Hagan, Ronan
• Format: Journal Article
• Language: English
• Published: 01.12.2009
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.FBCR09-A73

Abstract Notch signaling plays an integral role in cell growth and differentiation. Alterations in Notch signaling caused by mutations in receptors, amplification of pathway components, and increased expression of receptors and ligands have been shown to be important in tumor growth and maintenance. There are multiple Notch receptors and multiple ligands that can potentially interact to elicit a signal. Furthermore, many tumor cells express more than one Notch receptor. The complexity of these interactions and the potential specificity of resultant signals necessitate further understanding of the context of signaling to better determine how to treat Notch driven tumors. To this end, we have developed cell based reporter assays to investigate total Notch signal from cells stimulated by cell surface ligands in a co-culture system or by plate-bound ligands. In addition, we have developed assays to determine signal from individual Notch receptors. Human cancer cell lines that express multiple Notch receptors were engineered to express a Notch-dependent luciferase reporter. These cells were stimulated with plate-bound or cell surface ligands and assayed for activation of the Notch receptors. Subsequently, specific blocking of individual Notch receptors with antibodies was used to determine which specific receptors acted as effectors of Notch signal. Understanding both the array of Notch receptors on a particular cell type and more specifically the ability of each receptor to produce active signal will be important in determining how to effectively treat Notch driven tumors. Citation Information: Cancer Res 2009;69(23 Suppl):A73.