کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2108027 1083715 2014 17 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Oncogenic Kras Activates a Hematopoietic-to-Epithelial IL-17 Signaling Axis in Preinvasive Pancreatic Neoplasia
چکیده انگلیسی


• IL-17+ T cells are recruited to the pancreas in response to Kras and inflammation
• IL-17A overexpression accelerates PanIN initiation and progression
• Inhibition of IL-17 signaling effectively prevents PanIN initiation and progression
• Kras activates expression of functional IL-17 receptors on PanIN epithelium

SummaryMany human cancers are dramatically accelerated by 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 epithelial cells and also stimulates infiltration of the pancreatic stroma by IL-17-producing immune cells. Both effects are augmented by associated chronic pancreatitis, resulting in functional in vivo changes in PanIN epithelial gene expression. 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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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 25, Issue 5, 12 May 2014, Pages 621–637
نویسندگان
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