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Cell Lines

KPC Cell Line (mixed genetic background)

Invented by Dr Jen Morton from Cancer Research UK Glasgow: The Beatson Institute
Invented at Cancer Research UK Glasgow: The Beatson Institute
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Catalogue Number 153600
Antigen/Gene or Protein Targets Pdx1- Cre, lox-stop-lox-KrasG12D/+, lox-stop-lox-tp53R172H/+
Synonyms 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
Host Mouse
Disease Keywords Pancreatic cancer; pancreatic ductal adenocarcinoma
Model Transgenic
Relevance 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.
Conditional No
Research Area Cancer, Drug Discovery & Development
Notes These cells are from mice with a mixed genetic background
KPC Subtype: C57Bl6/J

References

There are 4 reference entries for this reagent.

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References: 4 entries

Li et al. 2014. Gastroenterology. 146(5):1386-96.e1-17. PMID: 24462734.

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Fascin is regulated by slug, promotes progression of pancreatic cancer in mice, and is associated with patient outcomes.

Europe PMC ID: 24462734

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Hingorani et al. 2005. Cancer Cell. 7(5):469-83. PMID: 15894267.

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Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice.

Europe PMC ID: 15894267

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References: 4 entries

Li et al. 2014. Gastroenterology. 146(5):1386-96.e1-17. PMID: 24462734.

View  

Fascin is regulated by slug, promotes progression of pancreatic cancer in mice, and is associated with patient outcomes.

View  

Hingorani et al. 2005. Cancer Cell. 7(5):469-83. PMID: 15894267.

View  

Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice.

View  

Add a reference

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