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Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model
Open accessAbstract
Small cell lung cancer (SCLC) is a highly aggressive human tumor with a more than 95% mortality rate. Its ontogeny and molecular pathogenesis remains poorly understood. We established a mouse model for neuroendocrine (NE) lung tumors by conditional inactivation of Rb1 and Trp53 in mouse lung epithelial cells. Mice carrying conditional alleles for both Rb1 and Trp53 developed with high incidence aggressive lung tumors with striking morphologic and immunophenotypic similarities to SCLC. Most of these tumors, which we designate MSCLC (murine small cell lung carcinoma), diffusely spread through the lung and gave rise to extrapulmonary metastases. In our model, inactivation of both Rb1 and p53 was a prerequisite for the pathogenesis of SCLC.
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“RB is inactivated in more than 90% of human small-cell lung carcinomas (SCLC)”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [24]
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“mouse genetic studies have confirmed that RB is crucial in preventing the initiation of this lung cancer sub-type24”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [24]
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“When loss of Trp53 and Rb are combined, more tumours develop in mutant mice24,147–149 but it becomes difficult to dissect the respective roles of these two potent tumour suppressors.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [24]
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Metadata
- Authors
- Meuwissen, R., Linn, S. C., Linnoila, R. I., Zevenhoven, J., Mooi, W. J., & Berns, A.
- Affiliations
- The Netherlands Cancer Institute (NL)
- National Cancer Institute (US)
- Corresponding author
- Berns, Anton
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 4
- Issue
- 3
- Pages
- 181-189
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W1978286483
- Cited by
- 643
- References
- 49
- Citations by year
- 2026: 22 · 2025: 41 · 2024: 30 · 2023: 43 · 2022: 43 · 2021: 40 · 2020: 33 · 2019: 43 · 2018: 34 · 2017: 34 · 2016: 27 · 2015: 31 · 2014: 27 · 2013: 24 · 2012: 16
- FWCI
- 8.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- KWF Kankerbestrijding
- Topics
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Keywords
- small cell lung cancer, lung neuroendocrine tumors, Trp53, RB1, conditional knockout mice, carcinogenesis, p53, retinoblastoma protein, lung epithelial cells, metastasis, mouse model
- MeSH terms
- Animals, DNA-Binding Proteins, Lung Neoplasms, Mice, Transgenic, Transcription Factors, Gene Expression Regulation, Neoplastic, Genes, p53, Tumor Suppressor Protein p53, Retinoblastoma Protein, Carcinoma, Small Cell, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins
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