This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bassères, D. S.
Right arrow Articles by Tenen, D. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bassères, D. S.
Right arrow Articles by Tenen, D. G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2006, p. 1109-1123, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.1109-1123.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Respiratory Failure Due to Differentiation Arrest and Expansion of Alveolar Cells following Lung-Specific Loss of the Transcription Factor C/EBP{alpha} in Mice

Daniela S. Bassères ,1,{dagger},§ Elena Levantini,1,{dagger} Hongbin Ji,2 Stefano Monti,3 Shannon Elf,1 Tajhal Dayaram,1 Maris Fenyus,1 Olivier Kocher,1 Todd Golub,3 Kwok-kin Wong,2 Balazs Halmos,1,{ddagger} and Daniel G. Tenen1*

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts,1 Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts,2 Broad Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts3

Received 23 August 2005/ Returned for modification 12 October 2005/ Accepted 14 November 2005

The leucine zipper family transcription factor CCAAT enhancer binding protein alpha (C/EBP{alpha}) inhibits proliferation and promotes differentiation in various cell types. In this study, we show, using a lung-specific conditional mouse model of C/EBP{alpha} deletion, that loss of C/EBP{alpha} in the respiratory epithelium leads to respiratory failure at birth due to an arrest in the type II alveolar cell differentiation program. This differentiation arrest results in the lack of type I alveolar cells and differentiated surfactant-secreting type II alveolar cells. In addition to showing a block in type II cell differentiation, the neonatal lungs display increased numbers of proliferating cells and decreased numbers of apoptotic cells, leading to epithelial expansion and loss of airspace. Consistent with the phenotype observed, genes associated with alveolar maturation, survival, and proliferation were differentially expressed. Taken together, these results identify C/EBP{alpha} as a master regulator of airway epithelial maturation and suggest that the loss of C/EBP{alpha} could also be an important event in the multistep process of lung tumorigenesis. Furthermore, this study indicates that exploring the C/EBP{alpha} pathway might have therapeutic benefits for patients with respiratory distress syndromes.

* Corresponding author. Mailing address: Harvard Institutes of Medicine, Rm. 954, 77 Avenue Louis Pasteur, Boston, MA 02115. Phone: (617) 667-5561. Fax: (617) 667-3299. E-mail: dtenen{at}bidmc.harvard.edu.

Supplemental material for this article may be found at http://mcb.asm.org/.

{dagger} D. S. Bassères and E. Levantini contributed equally to this work.

§ Present address: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, N.C.

{ddagger} Present address: Ireland Cancer Center, Case Western Reserve University, Cleveland, Ohio.

Molecular and Cellular Biology, February 2006, p. 1109-1123, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.1109-1123.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Koschmieder, S., Halmos, B., Levantini, E., Tenen, D. G. (2009). Dysregulation of the C/EBP{alpha} Differentiation Pathway in Human Cancer. JCO 27: 619-628 [Abstract] [Full Text]  
  • Huang, G., Eisenberg, R., Yan, M., Monti, S., Lawrence, E., Fu, P., Walbroehl, J., Lowenberg, E., Golub, T., Merchan, J., Tenen, D. G., Markowitz, S. D., Halmos, B. (2008). 15-Hydroxyprostaglandin Dehydrogenase is a Target of Hepatocyte Nuclear Factor 3{beta} and a Tumor Suppressor in Lung Cancer. Cancer Res. 68: 5040-5048 [Abstract] [Full Text]  
  • Peacock, C. D., Watkins, D. N. (2008). Cancer Stem Cells and the Ontogeny of Lung Cancer. JCO 26: 2883-2889 [Abstract] [Full Text]  
  • Loomis, K. D., Zhu, S., Yoon, K., Johnson, P. F., Smart, R. C. (2007). Genetic Ablation of CCAAT/Enhancer Binding Protein {alpha} in Epidermis Reveals Its Role in Suppression of Epithelial Tumorigenesis. Cancer Res. 67: 6768-6776 [Abstract] [Full Text]  
  • Maeda, Y., Dave, V., Whitsett, J. A. (2007). Transcriptional Control of Lung Morphogenesis. Physiol. Rev. 87: 219-244 [Abstract] [Full Text]  
  • Berg, T., Didon, L., Nord, M. (2006). Ectopic expression of C/EBP{alpha} in the lung epithelium disrupts late lung development. Am. J. Physiol. Lung Cell. Mol. Physiol. 291: L683-L693 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»