KPC Cell Line (mixed genetic background)
- Name Jennifer Morton
- Institute Cancer Research UK, Glasgow Beatson Institute
Tool name: KPC Cell Line (mixed genetic background)
Tool type: Cell Lines
Tool sub-type: Continuous
Cancer type: Pancreatic cancer; Pancreatic cancer
Description: The KPC mouse is an established and clinically relevant model of pancreatic ductal adenocarcinoma (PDA) which develops many key features observed in human PDA including pancreatic intraepithelial neoplasia alongside a robust inflammatory reaction including exclusion of effector T cells. Metastases are observed in around 80% of KPC animals located primarily in the liver and lungs. Mutations in both KRAS and TP53genes are found in around 80% and 70% of all human PDAs respectively. Tumors present in KPC mice display many immunohistological markers of PDA as well as possessing complex genomic rearrangements a key sign of genomic instability. The co-morbidities, cachexia, jaundice and ascites, associated with human PDA are also observed in this model and most pancreatic tumors are resistant to chemotherapy.
The KPC mouse contains a conditional point mutation in the transformation related protein 53 gene (TP53R172H), and a point mutation in the KRAS gene (KRASG12D) both of which generate non-functional proteins. A lox-stop-lox termination sequence is encoded upstream of both mutated genes to prevent expression in the absence of Cre recombinase. PDX1 (pancreatic and duodenal homeobox 1) is a transcription factor necessary for pancreatic development. The PDX1 promoter enables expression of Cre recombinase in acini, islet and duct cells of the pancreas. Cre-mediated recombination excises the two lox-stop-lox termination sequences and enables expression of both oncogenes: KRASG12D and TP53R172H in pancreatic tissue. Tissues not expressing Cre recombinase remain functionally heterozygous of the KRAS and TRP53 loci.
Research area: Cancer; Drug development
Additional notes: These cells are from mice with a mixed genetic background
KPC Subtype: C57Bl6/J
- For Research Use Only
- • Li et al. 2014. Gastroenterology. 146(5):1386-96.e1-17. PMID: 24462734.
- • Fascin is regulated by slug, promotes progression of pancreatic cancer in mice, and is associated with patient outcomes.
- • Hingorani et al. 2005. Cancer Cell. 7(5):469-83. PMID: 15894267.
- • Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice.