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Contributor Information

  • Name Jen Morton
  • Institute Cancer Research UK, Glasgow Beatson Institute

Tool Details

  • Tool name: KPC Cell Line (mixed 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:
  • Organism: Mouse
  • Cancer type: Pancreatic cancer; pancreatic ductal adenocarcinoma
  • Disease: 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 Discovery & Development

  • For Research Use Only

Target Details

Application Details

Handling

  • Format: Frozen
  • Growth medium: They all grow in DMEM (+10% FCS, 1% L-Glut and 1% Pen/strep). They may take a wee bit of time coming back up, don’t panic, just be gentle with them.
  • Storage conditions: Liquid Nitrogen
  • Shipping conditions: Dry ice
  • Mycoplasma free: Yes
  • Biosafety level: 1

Documentation

  • Available on request

References

  •   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.