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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 03, 2016 |
| Title |
Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Many human cancers are dramatically accelerated in the setting of chronic inflammation. However the specific cellular and molecular elements mediating this effect remain largely unknown. Using a murine model of pancreatic intraepithelial neoplasia (PanIN), we found that KrasG12D induces expression of functional IL-17 receptors on PanIN cells, and stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by chronic pancreatitis, resulting in functional in vivo changes in gene expression among PanIN epithelial cells. Forced IL-17 overexpression dramatically accelerates PanIN initiation and progression, while inhibition of IL-17 signaling using genetic or pharmacologic techniques effectively prevents PanIN formation. Together, these studies suggest that a hematopoietic-to-epithelial IL-17 signaling axis is a potent and requisite driver of PanIN formation.
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| Overall design |
In order to assess the functionality of IL-17 receptors on oncogenic pancreatic epithelium, we treated KCiMist1G + CP mice that had already developed mPanIN lesions with a cocktail of monoclonal antibodies directed against the IL-17 Receptor A (IL-17RA) and the cytokines IL-17A and IL-17F. Beginning at 6 weeks following Kras activation, antibodies were administered by two IP injections during the week prior to sacrifice (Figure 7A). At week 7 mice were sacrificed and GFP+ mPanIN epithelial cells were isolated by FACS. Microarray-based whole transcriptome expression analysis was performed comparing profiles from GFP+ cells sorted from mice that had received IL-17 neutralizing antibodies versus mice that received IgG isotype control antibodies.
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| Contributor(s) |
McAllister F, Bailey JM, Alsina J, Nirschl CJ, Sharma R, Fan H, Rattigan Y, Roeser JC, Lankapalli RH, Zhang H, Jaffee EM, Drake CG, Housseau F, Maitra A, Kolls JK, Sears CL, Pardoll DM, Leach SD |
| Citation(s) |
24823639 |
| Submission date |
Feb 06, 2014 |
| Last update date |
Mar 06, 2018 |
| Contact name |
Florencia McAllister, MD |
| Organization name |
The Johns Hopkins University
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| Department |
Sidney Kimmel Comprehensive Cancer Center
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| Lab |
The Harry and Jeanette Weinberg Building, Ste. 1100
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| Street address |
401 N. Broadway
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21287 |
| Country |
USA |
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| Platforms (1) |
| GPL6096 |
[MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA237551 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE54753_RAW.tar |
127.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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