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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 not altered in human lung adenocarcinoma.(A) mRNA expression of CEBPA, CEBPB, and CDKN2A in TCGA lung adenocarcinoma dataset. RSEM values obtained from TCGA data were log2 transformed and depicted as individual dots representing a sample and box plot. (B) Methylation status in CEBPA and CEBPB promoter regions in TCGA lung adenocarcinoma dataset. Scatter plot depicts mRNA expression in Y-axis and methylation level of the promoter region in X-axis of CEBPA and CEBPB genes. (C) Copy number estimates of CEBPA and CEBPB gene loci in TCGA lung adenocarcinoma dataset. Scatter plot depicts mRNA expression in Y-axis and copy number estimates in log2 scale in X-axis of CEBPA and CEBPB genes.
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pone.0120647.g006: C/EBPβ is not altered in human lung adenocarcinoma.(A) mRNA expression of CEBPA, CEBPB, and CDKN2A in TCGA lung adenocarcinoma dataset. RSEM values obtained from TCGA data were log2 transformed and depicted as individual dots representing a sample and box plot. (B) Methylation status in CEBPA and CEBPB promoter regions in TCGA lung adenocarcinoma dataset. Scatter plot depicts mRNA expression in Y-axis and methylation level of the promoter region in X-axis of CEBPA and CEBPB genes. (C) Copy number estimates of CEBPA and CEBPB gene loci in TCGA lung adenocarcinoma dataset. Scatter plot depicts mRNA expression in Y-axis and copy number estimates in log2 scale in X-axis of CEBPA and CEBPB genes.

Mentions: Lastly, we sought to determine whether C/EBPβ expression is altered in human lung adenocarcinoma using data from The Cancer Genome Atlas (TCGA). We confirmed that two tumor suppressors, CEBPA and CDKN2A, were downregulated in a subset of human lung adenocarcinomas as previously described [34, 35]. Compared to these two genes, expression of CEBPB was maintained in these tumor samples (Fig. 6A). Next, we examined the methylation status of the CEBPA and CEBPB promoters. The CEBPB promoters were unmethylated in all lung adenocarcinoma samples with available methylation data (n = 185), whereas the CEBPA promoter regions were frequently aberrantly methylated, consistent with previous results [36] (Fig. 6B). By examining the matched copy number data, we found that the CEBPA and CEBPB loci were not subject to frequent deletion (Fig. 6C). Taken together, these data suggest that expression of C/EBPβ is not altered in human lung adenocarcinoma.


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 not altered in human lung adenocarcinoma.(A) mRNA expression of CEBPA, CEBPB, and CDKN2A in TCGA lung adenocarcinoma dataset. RSEM values obtained from TCGA data were log2 transformed and depicted as individual dots representing a sample and box plot. (B) Methylation status in CEBPA and CEBPB promoter regions in TCGA lung adenocarcinoma dataset. Scatter plot depicts mRNA expression in Y-axis and methylation level of the promoter region in X-axis of CEBPA and CEBPB genes. (C) Copy number estimates of CEBPA and CEBPB gene loci in TCGA lung adenocarcinoma dataset. Scatter plot depicts mRNA expression in Y-axis and copy number estimates in log2 scale in X-axis of CEBPA and CEBPB genes.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4358974&req=5

pone.0120647.g006: C/EBPβ is not altered in human lung adenocarcinoma.(A) mRNA expression of CEBPA, CEBPB, and CDKN2A in TCGA lung adenocarcinoma dataset. RSEM values obtained from TCGA data were log2 transformed and depicted as individual dots representing a sample and box plot. (B) Methylation status in CEBPA and CEBPB promoter regions in TCGA lung adenocarcinoma dataset. Scatter plot depicts mRNA expression in Y-axis and methylation level of the promoter region in X-axis of CEBPA and CEBPB genes. (C) Copy number estimates of CEBPA and CEBPB gene loci in TCGA lung adenocarcinoma dataset. Scatter plot depicts mRNA expression in Y-axis and copy number estimates in log2 scale in X-axis of CEBPA and CEBPB genes.
Mentions: Lastly, we sought to determine whether C/EBPβ expression is altered in human lung adenocarcinoma using data from The Cancer Genome Atlas (TCGA). We confirmed that two tumor suppressors, CEBPA and CDKN2A, were downregulated in a subset of human lung adenocarcinomas as previously described [34, 35]. Compared to these two genes, expression of CEBPB was maintained in these tumor samples (Fig. 6A). Next, we examined the methylation status of the CEBPA and CEBPB promoters. The CEBPB promoters were unmethylated in all lung adenocarcinoma samples with available methylation data (n = 185), whereas the CEBPA promoter regions were frequently aberrantly methylated, consistent with previous results [36] (Fig. 6B). By examining the matched copy number data, we found that the CEBPA and CEBPB loci were not subject to frequent deletion (Fig. 6C). Taken together, these data suggest that expression of C/EBPβ is not altered in human lung adenocarcinoma.

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