KPC Cell Line (C57/BL6 genetic background)
- Name Jen Morton
- Institute Cancer Research UK, Glasgow Beatson Institute
Tool name: KPC Cell Line (C57/BL6 genetic background)
Alternate names: PDAC; Pdx1-Cre, LSL-KrasG12D/+, LSL-Trp53R172H/+, KC, PC, KPC,GTPase KRas, K-Ras 2, Ki-Ras, c-K-ras, c-Ki-ras, transformation related protein 53, insulin promoter factor 1; pancreatic and duodenal homeobox 1, transformation related protein 53, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, C-K-RAS, K-RAS; lox-stop-lox; LSL
Tool type: Cell Lines
Parental cell line:
Cancer type: Pancreatic cancer; pancreatic ductal adenocarcinoma
Description: Established cell line used as a model of pancreatic ductal adenocarcinoma.
Background and Research Application
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. Tumours present in KPC mice display many immune-histological 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 tumours 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 Discovery & Development
- 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.