Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma.
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ABSTRACT:
SUBMITTER: Hanlon L
PROVIDER: S-EPMC2880196 | biostudies-literature | 2010 Jun
REPOSITORIES: biostudies-literature
Publications
Notch1 functions as a tumor suppressor in a model of K-ras-induced pancreatic ductal adenocarcinoma.
Hanlon Linda L Avila Jacqueline L JL Demarest Renée M RM Troutman Scott S Allen Megan M Ratti Francesca F Rustgi Anil K AK Stanger Ben Z BZ Radtke Fred F Adsay Volkan V Long Fenella F Capobianco Anthony J AJ Kissil Joseph L JL
Cancer research 20100518 11
K-ras is the most commonly mutated oncogene in pancreatic cancer and its activation in murine models is sufficient to recapitulate the spectrum of lesions seen in human pancreatic ductal adenocarcinoma (PDAC). Recent studies suggest that Notch receptor signaling becomes reactivated in a subset of PDACs, leading to the hypothesis that Notch1 functions as an oncogene in this setting. To determine whether Notch1 is required for K-ras-induced tumorigenesis, we used a mouse model in which an oncogeni ...[more]
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2024-03-15 | PXD047878 | Pride
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Project description:STAG2 is targeted by somatic aberrations in a subset (4%) of human PDAs. Transposon mediated disruption of STAG2 in a KRASG12D genetically engineered mouse model promotes the development of PDA and its progression to metastatic disease. There was a statistically significant loss of STAG2 protein expression in human tumor tissue (Wilcoxon-Rank test) with complete absence of STAG2 staining observed in 15 (4.3%) patients. In univariate Kaplan Meier analysis nearly complete STAG2 positive staining (> 95% of nuclei positive) was associated with a median survival benefit of 6.41 months (p = 0.031). The survival benefit of adjuvant chemotherapy was only seen in patients with a STAG2 staining of less than 95% (median survival benefit 7.65 months; p = 0.028). Multivariate Cox Regression analysis showed that STAG2 is an independent prognostic factor for survival in pancreatic cancer patients. Finally we show that RNAi mediated knockdown of STAG2 selectively sensitizes human PDA cell lines to platinum-based therapy.
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