Priority Research Papers:
IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth
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Abstract
Michael Ayars1, Eileen O’Sullivan1, Anne Macgregor-Das1, Koji Shindo1, Haeryoung Kim1, Michael Borges1, Jun Yu1, Ralph H. Hruban1,2 and Michael Goggins1,2,3
1 Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
2 Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
3 Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Correspondence to:
Michael Goggins, email:
Keywords: pancreatic cancer, PanIN, RNA-seq, IL2RG, JAK3
Abbreviations: PanIN, pancreatic intraepithelial neoplasia; Il2Rγ, IL2 gamma receptor; IL, interleukin; GMCSF, granulocyte/macrophage colony stimulating factor
Received: May 19, 2017 Accepted: July 06, 2017 Published: August 03, 2017
Abstract
Pancreatic ductal adenocarcinoma evolves from precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). We performed RNA-sequencing analysis of laser capture microdissected PanINs and normal pancreatic duct cells to identify differentially expressed genes between PanINs and normal pancreatic duct, and between low-grade and high-grade PanINs. One of the most highly overexpressed transcripts identified in PanIN is interleukin-2 receptor subunit gamma (IL2RG) encoding the common gamma chain, IL2Rγ. CRISPR-mediated knockout of IL2RG in orthotopically implanted pancreatic cancer cells resulted in attenuated tumor growth in mice and reduced JAK3 expression in orthotopic tumors. These results indicate that IL2Rγ/JAK3 signaling contributes to pancreatic cancer cell growth in vivo.
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