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- Title
Metastatic Pancreatic Cancer Is Dependent on Oncogenic Kras in Mice.
- Authors
Collins, Meredith A.; Brisset, Jean-Christophe; Yaqing Zhang; Bednar, Filip; Pierre, Josette; Heist, Kevin A.; Galbán, Craig J.; Galbán, Stefanie; di Magliano, Marina Pasca
- Abstract
Pancreatic cancer is one of the deadliest human malignancies, and its prognosis has not improved over the past 40 years. Mouse models that spontaneously develop pancreatic adenocarcinoma and mimic the progression of the human disease are emerging as a new tool to investigate the basic biology of this disease and identify potential therapeutic targets. Here, we describe a new model of metastatic pancreatic adenocarcinoma based on pancreas-specific, inducible and reversible expression of an oncogenic form of Kras, together with pancreas-specific expression of a mutant form of the tumor suppressor p53. Using high-resolution magnetic resonance imaging to follow individual animals in longitudinal studies, we show that both primary and metastatic lesions depend on continuous Kras activity for their maintenance. However, reactivation of Kras" following prolonged inactivation leads to rapid tumor relapse, raising the concern that Kras"-resistance might eventually be acquired. Thus, our data identifies Kras" as a key oncogene in pancreatic cancer maintenance, but raises the possibility of acquired resistance should Kras inhibitors become available for use in pancreatic cancer.
- Subjects
PANCREATIC cancer; LABORATORY mice; P53 protein; MAGNETIC resonance imaging; ADENOCARCINOMA; DISEASE relapse
- Publication
PLoS ONE, 2012, Vol 7, Issue 12, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0049707