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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

Deletion of Cebpb has no effect on lung structure, but leads to aggregation of lymphoid cells in the lung.(A) Immunoblots of lung extracts from Cebpb+/+ or Cebpb-/- mice. Note that the predominant isoform expressed in mouse lungs is LAP and C/EBPβ expression in the lung is effectively lost in Cebpb-/- mice. (B) Representative images of hematoxylin and eosin staining of lungs isolated from Cebpb+/+ (I and II) and Cebpb-/- (III and IV) mice. We analyzed 10 Cebpb+/+ and 8 Cebpb-/- mice. Scale bars = 500 μm (I and III) and 100 μm (II and IV). Arrows indicate scattered lymphocyte aggregates in the lung parenchyma of a Cebpb-/- mouse. No gross or histologic architectural abnormalities were observed in the lungs of Cebpb-/- mice.
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pone.0120647.g002: Deletion of Cebpb has no effect on lung structure, but leads to aggregation of lymphoid cells in the lung.(A) Immunoblots of lung extracts from Cebpb+/+ or Cebpb-/- mice. Note that the predominant isoform expressed in mouse lungs is LAP and C/EBPβ expression in the lung is effectively lost in Cebpb-/- mice. (B) Representative images of hematoxylin and eosin staining of lungs isolated from Cebpb+/+ (I and II) and Cebpb-/- (III and IV) mice. We analyzed 10 Cebpb+/+ and 8 Cebpb-/- mice. Scale bars = 500 μm (I and III) and 100 μm (II and IV). Arrows indicate scattered lymphocyte aggregates in the lung parenchyma of a Cebpb-/- mouse. No gross or histologic architectural abnormalities were observed in the lungs of Cebpb-/- mice.

Mentions: Cebpb knockout mice have been reported to manifest no histological abnormalities in the lung at perinatal stage [23, 24]. Therefore, we sought to determine whether C/EBPβ is required for development and maintenance of lung at later adult stage. Lungs were isolated from Cebpb knockout and control mice up to 10 weeks of age. We confirmed C/EBPβ was not expressed in the lungs of Cebpb knockout mice (Fig. 2A), but gross appearance of the lungs was indistinguishable from those of Cebpb wild type mice (data not shown). Histological analysis revealed scattered parenchymal lymphoid aggregates in 7 out of 8 (87.5%) lungs isolated from Cebpb knockout mice, while no such aggregates were observed in ones from wild type siblings (0/10; 0%). However, no major difference in lung parenchymal architecture was apparent between C/EBPβ knockout and wild type mice (Fig. 2B).


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)

Deletion of Cebpb has no effect on lung structure, but leads to aggregation of lymphoid cells in the lung.(A) Immunoblots of lung extracts from Cebpb+/+ or Cebpb-/- mice. Note that the predominant isoform expressed in mouse lungs is LAP and C/EBPβ expression in the lung is effectively lost in Cebpb-/- mice. (B) Representative images of hematoxylin and eosin staining of lungs isolated from Cebpb+/+ (I and II) and Cebpb-/- (III and IV) mice. We analyzed 10 Cebpb+/+ and 8 Cebpb-/- mice. Scale bars = 500 μm (I and III) and 100 μm (II and IV). Arrows indicate scattered lymphocyte aggregates in the lung parenchyma of a Cebpb-/- mouse. No gross or histologic architectural abnormalities were observed in the lungs of Cebpb-/- mice.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4358974&req=5

pone.0120647.g002: Deletion of Cebpb has no effect on lung structure, but leads to aggregation of lymphoid cells in the lung.(A) Immunoblots of lung extracts from Cebpb+/+ or Cebpb-/- mice. Note that the predominant isoform expressed in mouse lungs is LAP and C/EBPβ expression in the lung is effectively lost in Cebpb-/- mice. (B) Representative images of hematoxylin and eosin staining of lungs isolated from Cebpb+/+ (I and II) and Cebpb-/- (III and IV) mice. We analyzed 10 Cebpb+/+ and 8 Cebpb-/- mice. Scale bars = 500 μm (I and III) and 100 μm (II and IV). Arrows indicate scattered lymphocyte aggregates in the lung parenchyma of a Cebpb-/- mouse. No gross or histologic architectural abnormalities were observed in the lungs of Cebpb-/- mice.
Mentions: Cebpb knockout mice have been reported to manifest no histological abnormalities in the lung at perinatal stage [23, 24]. Therefore, we sought to determine whether C/EBPβ is required for development and maintenance of lung at later adult stage. Lungs were isolated from Cebpb knockout and control mice up to 10 weeks of age. We confirmed C/EBPβ was not expressed in the lungs of Cebpb knockout mice (Fig. 2A), but gross appearance of the lungs was indistinguishable from those of Cebpb wild type mice (data not shown). Histological analysis revealed scattered parenchymal lymphoid aggregates in 7 out of 8 (87.5%) lungs isolated from Cebpb knockout mice, while no such aggregates were observed in ones from wild type siblings (0/10; 0%). However, no major difference in lung parenchymal architecture was apparent between C/EBPβ knockout and wild type mice (Fig. 2B).

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