Abstract
Pancreatic ductal adenocarcinoma evolves from precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). We performed RNAsequencing 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 83370-83383 |
| Number of pages | 14 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 48 |
| DOIs | |
| State | Published - 2017 |
Funding
This work was supported by NIH grants U01CA210170, CA62924 and CA176828, Susan Wojcicki, Dennis Troper and the Rolfe Pancreatic Cancer Foundation. MG is the Sol Goldman Professor of Pancreatic Cancer Research.
| Funders | Funder number |
|---|---|
| Rolfe Pancreatic Cancer Foundation | |
| Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health | CA62924, CA176828 |
| National Institute of Health-National Cancer Institute | U01CA210170 |
Keywords
- IL2RG
- JAK3
- PanIN
- Pancreatic cancer
- RNA-seq
ASJC Scopus subject areas
- Oncology
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