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CCAAT/enhancer binding protein β is dispensable for development of lung adenocarcinoma.

Cai Y, Hirata A, Nakayama S, VanderLaan PA, Levantini E, Yamamoto M, Hirai H, Wong KK, Costa DB, Watanabe H, Kobayashi SS - PLoS ONE (2015)

Bottom Line: 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.Taken together, our data suggest that C/EBPβ is dispensable for development of lung adenocarcinoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus

C/EBPβ is expressed in human lung cells.(A) Expression of CEBPB in various human tissues in the dataset from GTEx project. RPKM values were log2 transformed and presented as a box plot for each tissue type. (B) Protein extracts were isolated from a panel of human lung adenocarcinoma cell lines as well as an immortalized human bronchoepithelial cell line, BEAS-2B and subjected to Western blotting.
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pone.0120647.g001: C/EBPβ is expressed in human lung cells.(A) Expression of CEBPB in various human tissues in the dataset from GTEx project. RPKM values were log2 transformed and presented as a box plot for each tissue type. (B) Protein extracts were isolated from a panel of human lung adenocarcinoma cell lines as well as an immortalized human bronchoepithelial cell line, BEAS-2B and subjected to Western blotting.

Mentions: C/EBPβ regulates cellular proliferation and differentiation under normal physiological conditions. Thus, to confirm C/EBPβ is expressed in human lungs as well as rodent lungs [21, 22], we examined its expression level from various human organ systems from GTEx datasets. We found that CEBPB is expressed in human lung at a lower level than hematopoietic system but a level comparable to or higher than that in any other tissues examined (Fig. 1A). At a protein level, we also found that C/EBPβ expression was readily detected in BEAS-2B immortalized human bronchial epithelial cells [31] and a panel of human adenocarcinoma cell lines at variable but equivalent level (Fig. 1B). These results indicate that C/EBPβ is expressed in both benign and malignant cells of the lung.


CCAAT/enhancer binding protein β is dispensable for development of lung adenocarcinoma.

Cai Y, Hirata A, Nakayama S, VanderLaan PA, Levantini E, Yamamoto M, Hirai H, Wong KK, Costa DB, Watanabe H, Kobayashi SS - PLoS ONE (2015)

C/EBPβ is expressed in human lung cells.(A) Expression of CEBPB in various human tissues in the dataset from GTEx project. RPKM values were log2 transformed and presented as a box plot for each tissue type. (B) Protein extracts were isolated from a panel of human lung adenocarcinoma cell lines as well as an immortalized human bronchoepithelial cell line, BEAS-2B and subjected to Western blotting.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358974&req=5

pone.0120647.g001: C/EBPβ is expressed in human lung cells.(A) Expression of CEBPB in various human tissues in the dataset from GTEx project. RPKM values were log2 transformed and presented as a box plot for each tissue type. (B) Protein extracts were isolated from a panel of human lung adenocarcinoma cell lines as well as an immortalized human bronchoepithelial cell line, BEAS-2B and subjected to Western blotting.
Mentions: C/EBPβ regulates cellular proliferation and differentiation under normal physiological conditions. Thus, to confirm C/EBPβ is expressed in human lungs as well as rodent lungs [21, 22], we examined its expression level from various human organ systems from GTEx datasets. We found that CEBPB is expressed in human lung at a lower level than hematopoietic system but a level comparable to or higher than that in any other tissues examined (Fig. 1A). At a protein level, we also found that C/EBPβ expression was readily detected in BEAS-2B immortalized human bronchial epithelial cells [31] and a panel of human adenocarcinoma cell lines at variable but equivalent level (Fig. 1B). These results indicate that C/EBPβ is expressed in both benign and malignant cells of the lung.

Bottom Line: 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.Taken together, our data suggest that C/EBPβ is dispensable for development of lung adenocarcinoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America.

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.

No MeSH data available.


Related in: MedlinePlus