کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10757811 | 1050398 | 2013 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Trisomy of the Dscr1 gene suppresses early progression of pancreatic intraepithelial neoplasia driven by oncogenic Kras
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کلمات کلیدی
CDKNFATPDADYRK1Ap15Ink4bDSCR1CK-19Pancreatic ductal adenocarcinoma - آدنوکارسینوم پانکراس داکتالTUNEL - تونلPancreatic cancer - سرطان پانکراسDown syndrome - سندرم داونcytokeratin-19 - سیتوکراتین-19nuclear factor of activated T-cells - عامل هسته سلول های فعال شده فعال استpancreatic intraepithelial neoplasia - نئوپلاسی داخل پاتوسی پانکراسPanIN - پانینcyclin-dependent kinase - کییناز وابسته به سیکلین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Individuals with Down syndrome exhibit remarkably reduced incidence of most solid tumors including pancreatic cancer. Multiple mechanisms arising from the genetic complexity underlying Down syndrome has been suggested to contribute to such a broad cancer protection. In this study, utilizing a genetically engineered mouse model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia-1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN lesions mediated by oncogenic KrasG12D. In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15Ink4b tumor suppressor and reduction of cell proliferation in early PanIN lesions. Our data suggest that attenuation of calcineurin-NFAT signaling in neoplastic pancreatic ductal epithelium by a single extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN lesions driven by oncogenic Kras, and thus may be a potential mechanism underlying reduced incidence of pancreatic cancer in Down syndrome individuals.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 440, Issue 1, 11 October 2013, Pages 50-55
Journal: Biochemical and Biophysical Research Communications - Volume 440, Issue 1, 11 October 2013, Pages 50-55
نویسندگان
Jang Choon Lee, Jimin Shin, Kwan-Hyuck Baek,