Metastatic Pancreatic Cancer Is Dependent on Oncogenic Kras in Mice

Autor: Marina Pasca di Magliano, Filip Bednar, Yaqing Zhang, Kevin A. Heist, Meredith A. Collins, Craig J. Galbán, Josette Pierre, Stefanie Galbán, Jean-Christophe Brisset
Rok vydání: 2012
Předmět:
Oncology
Mouse
lcsh:Medicine
medicine.disease_cause
Polymerase Chain Reaction
Metastasis
Mice
0302 clinical medicine
Molecular Cell Biology
Gastrointestinal Cancers
Basic Cancer Research
Signaling in Cellular Processes
Neoplasm Metastasis
lcsh:Science
0303 health sciences
Multidisciplinary
Animal Models
Immunohistochemistry
Magnetic Resonance Imaging
3. Good health
medicine.anatomical_structure
030220 oncology & carcinogenesis
Medicine
Adenocarcinoma
KRAS
Pancreas
Research Article
Signal Transduction
medicine.medical_specialty
Blotting
Western
Ras Signaling
Gastroenterology and Hepatology
Pancreatic Cancer
03 medical and health sciences
Model Organisms
Pancreatic cancer
Internal medicine
Gastrointestinal Tumors
Genetics
Cancer Genetics
medicine
Animals
Biology
030304 developmental biology
Oncogene
business.industry
lcsh:R
Cancers and Neoplasms
Metastatic Pancreatic Adenocarcinoma
medicine.disease
digestive system diseases
Pancreatic Neoplasms
Genes
ras
lcsh:Q
business
Carcinogenesis
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 12, p e49707 (2012)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0049707
Popis: 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, re-activation 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.
Databáze: OpenAIRE
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