Cited by 645Lung Cancer Research StudiesCancer-related Molecular PathwaysOccupational and environmental lung diseases

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Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model

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Meuwissen, Ralph, Linn, Sabine C, Linnoila, R.Ilona, Zevenhoven, John, Mooi, Wolter J, Berns, Anton·2003·Cancer Cell

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Abstract

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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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
ORCID: Meuwissen, Ralph
Linn, Sabine C
Berns, Anton
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2003-09
Volume: 4
Issue: 3
Pages: 181-189
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/s1535-6108(03)00220-4
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 3607 d)
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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Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model

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