IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth

被引:19
作者
Ayars, Michael [1 ]
O'Sullivan, Eileen [1 ]
Macgregor-Das, Anne [1 ]
Shindo, Koji [1 ]
Kim, Haeryoung [1 ]
Borges, Michael [1 ]
Yu, Jun [1 ]
Hruban, Ralph H. [1 ,2 ]
Goggins, Michael [1 ,2 ,3 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Oncol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA
关键词
pancreatic cancer; PanIN; RNA-seq; IL2RG; JAK3; PRECURSOR LESIONS; EXPRESSION; CHAIN; BETA; REGULATOR; TP53;
D O I
10.18632/oncotarget.19848
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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, IL2R gamma. 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 IL2R gamma/JAK3 signaling contributes to pancreatic cancer cell growth in vivo.
引用
收藏
页码:83370 / 83383
页数:14
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