CDKN2B deletion is essential for pancreatic cancer development instead of unmeaningful co-deletion due to juxtaposition to CDKN2A
Open accessAbstract
Pancreatic cancer is among the deadliest malignancies; however, the genetic events that lead to pancreatic carcinogenesis in adults remain unclear. In vivo models in which these genetic alterations occur in adult animals may more accurately reflect the features of human cancer. In this study, we demonstrate that inactivation of Cdkn2b (p15ink4b) is necessary for induction of pancreatic cancer by oncogenic KRAS G12D expression and inactivation of Tp53 and Cdkn2a in adult mouse pancreatic ductal cells (P60 or older). KRAS G12D overexpression in these cells activated transforming growth factor-β signaling and expression of CDKN2B, which, along with CDKN2A, led to cellular senescence and protected cells from KRAS-mediated transformation via inhibition of retinoblastoma phosphorylation. These results show a critical role of CDKN2B inactivation in pancreatic carcinogenesis, and provide a useful adult animal model by genetic engineering via lentiviral delivery.
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CDKN2B deletion, rather than CDKN2A, plays a crucial role in inducing pancreatic cancer in a mouse model.
“Contrary to prior beliefs, the study found that CDKN2B, rather than CDKN2A, plays a crucial role in inducing pancreatic cancer. Deletion of CDKN2B, encoding p15INK4B, was identified as essential for tumorigenesis in a mouse model.”
From Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer (2024) · cites this paper as [39]
The Abstract and Introduction identify Cdkn2b inactivation as necessary for pancreatic cancer induction in this adult mouse model. But the Results (‘Induction of pancreatic cancer in adult mice’) report tumors only when Cdkn2a and Cdkn2b were both inactivated, alongside oncogenic KRAS and Tp53 inactivation. Thus ‘rather than CDKN2A’ overstates the distinction; page numbers are not provided in our copy. (LLM, conf=0.88)
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- Authors
- Tu, Q., Hao, J., Zhou, X., Yan, L., Dai, H., Sun, B., Yang, D., An, S., Lv, L., Jiao, B., Chen, C., Lai, R., Shi, P., & Zhao, X.
- Affiliations
- Kunming Institute of Zoology (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Shi, P
- Zhao, X
- Venue
- Oncogene
- Published
- 2017-09-11
- Volume
- 37
- Issue
- 1
- Pages
- 128-138
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC5759028
- OpenAlex
- W2755727917
- Cited by
- 66
- References
- 51
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 9 · 2023: 7 · 2022: 15 · 2021: 13 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 2
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Oncogene (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81472862)
- Chinese Academy of Sciences (XDB13020400, 2012HA014, XDA 01040403)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- CDKN2B, CDKN2A, pancreatic cancer, pancreatic carcinogenesis, KRAS G12D, TP53, cellular senescence, retinoblastoma protein phosphorylation, TGF-beta signaling, lentiviral gene delivery, tumor suppressor inactivation
- MeSH terms
- Animals, Genetic Engineering, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Neoplasms, Experimental, Pancreatic Neoplasms, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Retinoblastoma Protein, Proto-Oncogene Proteins p21(ras), Cellular Senescence, Sequence Deletion, Cyclin-Dependent Kinase Inhibitor p16, RNA, Small Interfering, Cell Line, Tumor, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p15, Cyclin-Dependent Kinase Inhibitor p18, Mice, Carcinogenesis
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