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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Mol+Cell+Biol 2018 ; 38 (3): ä Nephropedia Template TP
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Elevated HuR in Pancreas Promotes a Pancreatitis-Like Inflammatory Microenvironment That Facilitates Tumor Development #MMPMID29133460
Peng W; Furuuchi N; Aslanukova L; Huang YH; Brown SZ; Jiang W; Addya S; Vishwakarma V; Peters E; Brody JR; Dixon DA; Sawicki JA
Mol Cell Biol 2018[Feb]; 38 (3): ä PMID29133460show ga
Human antigen R (ELAVL1; HuR) is perhaps the best-characterized RNA-binding protein. Through its overexpression in various tumor types, HuR promotes posttranscriptional regulation of target genes in multiple core signaling pathways associated with tumor progression. The role of HuR overexpression in pancreatic tumorigenesis is unknown and led us to explore the consequences of HuR overexpression using a novel transgenic mouse model that has a >2-fold elevation of pancreatic HuR expression. Histologically, HuR-overexpressing pancreas displays a fibroinflammatory response and other pathological features characteristic of chronic pancreatitis. This pathology is reflected in changes in the pancreatic gene expression profile due, in part, to genes whose expression changes as a consequence of direct binding of their respective mRNAs to HuR. Older mice develop pancreatic steatosis and severe glucose intolerance. Elevated HuR cooperated with mutant K-rasG12D to result in a 3.4-fold increase in pancreatic ductal adenocarcinoma (PDAC) incidence compared to PDAC presence in K-rasG12D alone. These findings implicate HuR as a facilitator of pancreatic tumorigenesis, especially in the setting of inflammation, and a novel therapeutic target for pancreatitis treatment.