ArticlePloS one2013
CCAAT/enhancer-binding protein-α suppresses lung tumor development in mice through the p38α MAP kinase pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- HOXB8 promotes invasion and metastasis of high-grade serous ovarian cancer via suppression of the KDM6B/C/EBPα signaling axis.Translational cancer research · 2026Article
- A review of C/EBP α: a potential novel target for solid tumor intervention.Journal of translational medicine · 2025Review
- A comprehensive analysis of CEBPA on prognosis and function in uterine corpus endometrial carcinoma.Scientific reports · 2024Article
- Targeting CEBPA to restore cellular identity and tissue homeostasis in pulmonary fibrosis.JCI insight · 2024Article
- Dynamic interplay of nuclear receptors in tumor cell plasticity and drug resistance: Shifting gears in malignant transformations and applications in cancer therapeutics.Cancer metastasis reviews · 2024Review
- Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis.Biomedicines · 2023Article
- RNA Activation-A Novel Approach to Therapeutically Upregulate Gene Transcription.Molecules (Basel, Switzerland) · 2021Review
- Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway.Endocrinology and metabolism (Seoul, Korea) · 2021Article
- Effects of C/EBPα overexpression on alveolar epithelial type II cell proliferation, apoptosis and surfactant protein-C expression after exposure to hyperoxia.BMC pulmonary medicine · 2019Article
- Diallyl disulfide down-regulates calreticulin and promotes C/EBPα expression in differentiation of human leukaemia cells.Journal of cellular and molecular medicine · 2019Article
- Trichostatin A inhibits the activation of Hepatic stellate cells by Increasing C/EBP-α Acetylation in vivo and in vitro.Scientific reports · 2018Article
- Upregulation of C/EBPα contributes to colorectal cancer growth, metastasis and indicates poor survival outcome.American journal of cancer research · 2018Article
- Taurine ameliorates particulate matter-induced emphysema by switching on mitochondrial NADH dehydrogenase genes.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Review
- Fraction of MHCII and EpCAM expression characterizes distal lung epithelial cells for alveolar type 2 cell isolation.Respiratory research · 2017Article
- In silico identification of potential key regulatory factors in smoking-induced lung cancer.BMC medical genomics · 2017Article
- Review
- [The expression and role of the transcription factor C/EBPα in chronic myeloid leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2015Article
- LincRNA-uc002yug.2 involves in alternative splicing of RUNX1 and serves as a predictor for esophageal cancer and prognosis.Oncogene · 2015Article
- Protein networks in induced sputum from smokers and COPD patients.International journal of chronic obstructive pulmonary disease · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) is a basic leucine zipper transcription factor and is expressed in alveolar type II cells, alveolar macrophages and Clara cells in the lung. Although decrease or absence of C/EBPα expression in human non-small cell lung cancer suggests a possible role of C/EBPα as a lung tumor suppressor, there is no direct proof for this hypothesis. In this study, we investigated, for the first time, the role of C/EBPα in lung tumors in vivo using transgenic mice with lung epithelial specific conditional deletion of Cebpa (Cebpα(Δ/Δ) mice) and a urethane-induced lung tumor model. C/EBPα expression in the lung was dispensable, and its deletion was not oncogenic under unstressed conditions. However, at 28 wk after urethane injection, the number and size of tumors and the tumor burden were significantly higher in Cebpα(Δ/Δ) mice than in littermate control mice. Urethane-injected Cebpα(Δ/Δ) mice showed highly proliferative adenomas and adenocarcinomas in the lung, and survival time after urethane-injection was significantly shorter than that in control mice. In control mice, C/EBPα was strongly induced in the tumor tissues at 28 weeks after urethane-injection, but became weakened or absent as tumors progressed after long-term observation for over 1 year. Using intraperitoneal injection of p38 inhibitor (SB203580), we demonstrated that the induction of C/EBPα is strongly regulated by the p38 MAP kinase in murine alveolar epithelial cells. A high correlation was demonstrated between the expression of C/EBPα and p38α MAP kinase in tumor cells, suggesting that C/EBPα silencing in tumor cells is caused by down-regulation of p38α MAP kinase. In conclusion, the role of C/EBPα as a lung tumor suppressor was demonstrated for the first time in the present study, and the extinguished C/EBPα expression through p38α inactivation leads tumor promotion and progression.
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