Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma
Dana-Farber Cancer Institute · Harvard University · +6 more institutions
Abstract
Pancreatic ductal adenocarcinoma ranks among the most lethal of human malignancies. Here, we assess the cooperative interactions of two signature mutations in mice engineered to sustain pancreas-specific Cre-mediated activation of a mutant Kras allele (KrasG12D) and deletion of a conditional Ink4a/Arf tumor suppressor allele. The phenotypic impact of KrasG12D alone was limited primarily to the development of focal premalignant ductal lesions, termed pancreatic intraepithelial neoplasias (PanINs), whereas the sole inactivation of Ink4a/Arf failed to produce any neoplastic lesions in the pancreas. In combination, KrasG12D expression and Ink4a/Arf deficiency resulted in an earlier appearance of PanIN lesions and…
Citation impact
- FWCI
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- Percentile
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- References
- 84
Authors
8- AJAndrew J. AguirreCorresponding
Dana-Farber Cancer Institute
- NBNabeel Bardeesy
Harvard University, Harvard University Press, Dana-Farber Cancer Institute
- MSManisha Sinha
Harvard University, Harvard University Press, Dana-Farber Cancer Institute
- LVLyle V. Lopez
Harvard University, Harvard University Press, Dana-Farber Cancer Institute
- DADavid A. Tuveson
Cancer Research Institute, California University of Pennsylvania, UPMC Hillman Cancer Center, University of Pennsylvania
Topics & keywords
- Pancreatic Intraepithelial Neoplasia
- KRAS
- Biology
- Cancer research
- Pancreas
- Adenocarcinoma
- Pancreatic cancer
- Stromal cell
- Good health and well-being