• J. Gastrointest. Surg. · Jan 2012

    RAGE gene deletion inhibits the development and progression of ductal neoplasia and prolongs survival in a murine model of pancreatic cancer.

    • Joseph DiNorcia, Minna K Lee, Dorota N Moroziewicz, Megan Winner, Paritosh Suman, Fei Bao, Helen E Remotti, Yu Shan Zou, Shi Fang Yan, Wanglong Qiu, Gloria H Su, Ann Marie Schmidt, and John D Allendorf.
    • College of Physicians and Surgeons, Department of Surgery, Columbia University, 161 Fort Washington Avenue, Suite 820, New York, NY 10032-3784, USA.
    • J. Gastrointest. Surg. 2012 Jan 1; 16 (1): 104-12; discussion 112.

    BackgroundThe receptor for advanced glycation end-products (RAGE) is implicated in pancreatic tumorigenesis. Activating Kras mutations and p16 inactivation are genetic abnormalities most commonly detected as pancreatic ductal epithelium progresses from intraepithelial neoplasia (PanIN) to adenocarcinoma (PDAC).ObjectiveThe aim of this study was to evaluate the effect of RAGE (or AGER) deletion on the development of PanIN and PDAC in conditional Kras ( G12D ) mice.Materials And MethodsPdx1-Cre; LSL-Kras ( G12D/+) mice were crossed with RAGE (-/-) mice to generate Pdx1-Cre; LSL-Kras ( G12D/+) ; RAGE (-/-) mice. Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-) mice were crossed with RAGE (-/-) mice to generate Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice. Pancreatic ducts were scored and compared to the relevant RAGE (+/+) controls.ResultsAt 16 weeks of age, Pdx1-Cre; LSL-Kras ( G12D/+); RAGE (-/-) mice had significantly fewer high-grade PanIN lesions than Pdx1-Cre; LSL-Kras ( G12D/+); RAGE (+/+) controls. At 12 weeks of age, none of the Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice had PDAC compared to a 45.5% incidence of PDAC in Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (+/+) controls. Finally, Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice also displayed markedly longer median survival.ConclusionLoss of RAGE function inhibited the development of PanIN and progression to PDAC and significantly prolonged survival in these mouse models. Further work is needed to target the ligand-RAGE axis for possible early intervention and prophylaxis in patients at risk for developing pancreatic cancer.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…