Rgs16::GFP is a novel and early reporter of GPCR signaling during beta-cell expansion and pancreatic ductal adenocarcinoma (PDAC). Novel approaches are needed to understand the contributions of endocrine progenitors and b-cell regeneration during islet expansion, and to discover new therapeutics for diabetes that will not promote PDAC. G-protein signaling is an excellent target for therapeutics but is not well understood in pancreas development and disease. Regulators of G-protein signaling (RGS) proteins can serve as biomarkers for active G protein coupled receptor (GPCR) signaling. Rgs16 is expressed in pancreatic progenitor and endocrine cells during development, then extinguish in normal glycemic weanlings (DMM 3:567). Rgs16 is reactivated in models of diabetes and PDAC. RNA-Seq was used to identify 63 GPCRs (28 orphans) expressed in PDAC cells, whose expression profile is closely related to embryonic duct and endocrine progenitors. PDAC cells have been validated for 384-well high throughput screens (HTS). A putative GPCR-ligand stimulated Rgs16::GFP expression in 90% of PDAC cells, and in islets in a regenerative model of type 1 diabetes. Mouse models of diabetes and PDAC will be used to validate small molecules identified in HTS. Rgs16 may control islet progenitor cell activation, differentiation and migration during ductal and islet expansion in embryos and metabolically stressed adults.
Funding: NIH (GM61395) and Welch Foundation (I-1382) to TMW
Citation Format: Thomas M. Wilkie, Ozhan Ocal, Lee B. Rivera, Rolf A. Brekken. Rgs16: HTS biomarker for pancreas development, diabetes, and PDAC. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A98.