Inhibition of progression of PanIN through antagonizing EGFR
- 139 Downloads
Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor with high lethality in humans. Pancreatic intraepithelial neoplasia (PanIN) is the predominant precancerous lesion for PDAC. Although PanIN is frequently detected in the normal and inflamed pancreas, only a few of PanIN eventually progress into PDAC. Thus, inhibition of PanIN-to-PDAC conversion is critical for preventing the occurrence of PDAC. Here, we evaluated the effect of inhibition of epidermal growth factor receptor (EGFR) signaling on the progression of low-grade PanIN into high-grade PDAC in an established mouse PDAC model (Ptf1a-Cre; K-rasG12D). We found that intraductal infusion of EGFR inhibitors at 12 weeks of age, which induced sustained inhibition of EGFR signaling in the pancreas, significantly decreased the incidence of high-grade PanIN in these mice at 24 weeks of age. Thus, our study suggests that inhibition of EGFR signaling may prevent development of PDAC.
KeywordsPancreatic ductal adenocarcinoma (PDAC) Pancreatic intraepithelial neoplasia (PanIN) Epidermal growth factor receptor (EGFR)
Conflicts of interest
- 14.Perini MV, Montagnini AL, Coudry R, Patzina R, Penteado S, Abdo EE, Diniz A, Jukemura J, da Cunha JE. Prognostic significance of epidermal growth factor receptor overexpression in pancreas cancer and nodal metastasis. ANZ Journal of Surgery. 2013Google Scholar
- 22.Xiao X, Guo P, Prasadan K, Shiota C, Peirish L, Fischbach S, et al. Pancreatic cell tracing, lineage tagging and targeted genetic manipulations in multiple cell types using pancreatic ductal infusion of adeno-associated viral vectors and/or cell-tagging dyes. Nat Protoc. 2014;9:2719–24.CrossRefPubMedPubMedCentralGoogle Scholar