Human Pancreatic Duct Epithelial Cell Model for KRAS Transformation
Abstract
Mutations on the KRAS gene occur early during pancreatic duct cell carcinogenesis and have been identified in up to 90% of ductal adenocarcinoma. However, the functional role of KRAS mutations in the malignant transformation of normal pancreatic duct epithelial cells into cancer cells remains unknown. We have developed an in vitro model for KRAS transformation using near-normal HPV-16E6E7-immortalized human pancreatic ductal epithelial (HPDE-E6E7) cells. The expression of mutant KRAS(G12V) in HPDE cells by retroviral transduction resulted in weak tumorigenic transformation, with tumors formed in 50% of immune-deficient scid mice implanted by these KRAS-transformed cells. The model provides an opportunity to dissect further the molecular and cellular mechanisms associated with human pancreatic duct cell carcinogenesis.
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PDOs have emerged as a promising preclinical model for therapeutic prediction and functional studies across multiple cancer types, including in PDAC.
“PDOs have emerged as a promising preclinical model for therapeutic prediction and functional studies across multiple cancer types, including in PDAC18,19,48–50.”
From Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolution (2022) · cites this paper as [18]
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Occult polyclonality of preclinical pancreatic cancer models drives in vitro evolutionPreprint
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- Authors
- Radulovich, N., Qian, J., & Tsao, M.
- Affiliations
- University Health Network (CA)
- Venue
- Methods in Enzymology
- Publisher
- Elsevier
- Published
- 2008
- Volume
- 439
- Pages
- 1-13
- ISSN
- 0076-6879 (ISSN-L)
- OpenAlex
- W1542572330
- Cited by
- 39
- References
- 15
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 3 · 2015: 5 · 2014: 5 · 2013: 4 · 2012: 1
- FWCI
- 4.41
- Type
- book chapter
- Language
- en
- Open access
- closed
- Licence
- Locations
- Methods in enzymology on CD-ROM/Methods in enzymology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (MOP‐49585)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- KRAS mutation, pancreatic ductal adenocarcinoma, pancreatic duct cells, malignant transformation, KRAS G12V, retroviral transduction, tumorigenic transformation, in vitro carcinogenesis model, immunodeficient mice
- MeSH terms
- Cell Transformation, Neoplastic, Epithelial Cells, Humans, Pancreatic Ducts, Proto-Oncogene Proteins, Genes, ras, Proto-Oncogene Proteins p21(ras), ras Proteins, Cell Culture Techniques
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