Cited by 538Lung Cancer Research StudiesCancer-related Molecular PathwaysCancer Cells and Metastasis

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Cell of Origin of Small Cell Lung Cancer: Inactivation of Trp53 and Rb1 in Distinct Cell Types of Adult Mouse Lung

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Sutherland, Kate D., Proost, Natalie, Brouns, Inge, Adriaensen, Dirk, Song, Ji-Ying, Berns, Anton·2011·Cancer Cell

DOI 10.1016/j.ccr.2011.04.019

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Abstract

Small cell lung cancer (SCLC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we assessed the effect of Trp53 and Rb1 inactivation in distinct cell types in the adult lung using adenoviral vectors that target Cre recombinase to Clara, neuroendocrine (NE), and alveolar type 2 (SPC-expressing) cells. Using these cell type-restricted Adeno-Cre viruses, we show that loss of Trp53 and Rb1 can efficiently transform NE and SPC-expressing cells leading to SCLC, albeit SPC-expressing cells at a lesser efficiency. In contrast, Clara cells were largely resistant to transformation. The results indicate that although NE cells serve as the predominant cell of origin of SCLC a subset of SPC-expressing cells are also endowed with this ability.

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Authors: Sutherland, K. D., Proost, N., Brouns, I., Adriaensen, D., Song, J.-Y., & Berns, A.
Affiliations: The Netherlands Cancer Institute (NL)
University of Antwerp (BE)
Corresponding author: Berns, Anton
ORCID: Sutherland, Kate D.
Proost, Natalie
Brouns, Inge
Song, Ji-Ying
Berns, Anton
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2011-06
Volume: 19
Issue: 6
Pages: 754-764
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2011.04.019
OpenAlex: W1972570571
Cited by: 534
References: 48
Citations by year: 2026: 22 · 2025: 54 · 2024: 41 · 2023: 48 · 2022: 33 · 2021: 50 · 2020: 40 · 2019: 28 · 2018: 37 · 2017: 33 · 2016: 31 · 2015: 33 · 2014: 20 · 2013: 27 · 2012: 21
FWCI: 13.24
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 813 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Health and Medical Research Council (516781)
Fonds De La Recherche Scientifique - FNRS
National Institutes of Health
Topics: Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords: small cell lung cancer, cell of origin, RB1 inactivation, Clara cells, neuroendocrine cells, alveolar type II cells
MeSH terms: Adenoviridae, Animals, Cell Transformation, Neoplastic, Lung, Lung Neoplasms, Tumor Suppressor Protein p53, Retinoblastoma Protein, Integrases, Mice, Neuroendocrine Cells, Small Cell Lung Carcinoma

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Cell of Origin of Small Cell Lung Cancer: Inactivation of Trp53 and Rb1 in Distinct Cell Types of Adult Mouse Lung

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