Differential impact of the ERBB receptors EGFR and ERBB2 on the initiation of pancreatic intraepithelial neoplasia
(2020)
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- Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with a low survival rate. Pancreatic intraepithelial neoplasia (PanIN) correspond to a preinvasive lesion of PDAC and originate from acinar cells that undergo acinar-to-ductal metaplasia (ADM). Mutated KRAS plays a major role in the formation of these lesions. EGFR is required for KRAS-mediated PanIN development but little is known about the role of its preferred dimerization partner, ERBB2. To explore the role of ERBB2, we used mouse models deleted for ERBB2 with or without mutated KRAS in acinar cells. We found that, unlike EGFR, ERBB2 is not required for ADM or PanIN formation. We also used a mathematical model of EGFR-ERBB2-KRAS interactions that confirmed the essential impact of EGFR and predicted that ERBB2 impacts ERBB signaling only when overexpressed but not when its expression is decreased. In conclusion, EGFR and ERBB2 differentially control ERBB signaling during pancreatic tumorigenesis.
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Meyers, N. (2020). Differential impact of the ERBB receptors EGFR and ERBB2 on the initiation of pancreatic intraepithelial neoplasia. https://hdl.handle.net/2078.5/117667