title: CCAAT/enhancer binding protein β is dispensable for development of lung adenocarcinoma.
abstract: Lung cancer is the leading cause of cancer death worldwide. Although disruption of normal proliferation and differentiation is a vital component of tumorigenesis, the mechanisms of this process in lung cancer are still unclear. A transcription factor, C/EBPβ is a critical regulator of proliferation and/or differentiation in multiple tissues. In lung, C/EBPβ is expressed in alveolar pneumocytes and bronchial epithelial cells; however, its roles on normal lung homeostasis and lung cancer development have not been well described. Here we investigated whether C/EBPβ is required for normal lung development and whether its aberrant expression and/or activity contribute to lung tumorigenesis. We showed that C/EBPβ was expressed in both human normal pneumocytes and lung adenocarcinoma cell lines. We found that overall lung architecture was maintained in Cebpb knockout mice. Neither overexpression of nuclear C/EBPβ nor suppression of CEBPB expression had significant effects on cell proliferation. C/EBPβ expression and activity remained unchanged upon EGF stimulation. Furthermore, deletion of Cebpb had no impact on lung tumor burden in a lung specific, conditional mutant EGFR lung cancer mouse model. Analyses of data from The Cancer Genome Atlas (TCGA) revealed that expression, promoter methylation, or copy number of CEBPB was not significantly altered in human lung adenocarcinoma. Taken together, our data suggest that C/EBPβ is dispensable for development of lung adenocarcinoma.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America; Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Hirata
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Sohei
authors.initials: S
authors.lastname: Nakayama
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Paul A
authors.initials: PA
authors.lastname: VanderLaan
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America; Institute of Biomedical Technologies, National Research Council (CNR), Pisa, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Levantini
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of Transfusion Medicine & Cell Therapy, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Hirai
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Costa
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America; Cancer Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Hideo
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America; Harvard Stem Cell Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Susumu S
authors.initials: SS
authors.lastname: Kobayashi
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000503:physiopathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D015153:Blotting, Western; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism*; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D023081:CCAAT-Binding Factor; D008156:Luciferases