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CCAAT/enhancer-binding protein β: its role in breast cancer and associations with receptor tyrosine kinases

Published online by Cambridge University Press:  08 April 2009

Cynthia A. Zahnow*
Affiliation:
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Bunting-Blaustein Cancer Research Building, 1650 Orleans St, Baltimore, MD 21231-1000, USA. Tel: +1 410 955 8506; Fax: +1 410 614 9884; E-mail: [email protected]

Abstract

The CCAAT/enhancer-binding proteins (C/EBPs) are a family of leucine-zipper transcription factors that regulate gene expression to control cellular proliferation, differentiation, inflammation and metabolism. Encoded by an intronless gene, C/EBPβ is expressed as several distinct protein isoforms (LAP1, LAP2, LIP) whose expression is regulated by the differential use of several in-frame translation start sites. LAP1 and LAP2 are transcriptional activators and are associated with differentiation, whereas LIP is frequently elevated in proliferative tissue and acts as a dominant-negative inhibitor of transcription. However, emerging evidence suggests that LIP can serve as a transcriptional activator in some cellular contexts, and that LAP1 and LAP2 might also have unique actions. The LIP:LAP ratio is crucial for the maintenance of normal growth and development, and increases in this ratio lead to aggressive forms of breast cancer. This review discusses the regulation of C/EBPβ activity by post-translational modification, the individual actions of LAP1, LAP2 and LIP, and the functions and downstream targets that are unique to each isoform. The role of the C/EBPβ isoforms in breast cancer is discussed and emphasis is placed on their interactions with receptor tyrosine kinases.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2009

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References

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Further reading, resources and contacts

Information about breast cancer treatment, prevention, genetics, causes, screening, clinical trials, research and statistics from the National Cancer Institute can be found at:

White, A.W., Westwell, A.D. and Brahemi, G. (2008) Protein-protein interactions as targets for small molecule therapeutics. Expert Reviews in Molecular Medicine 10, 1-14CrossRefGoogle ScholarPubMed
White, A.W., Westwell, A.D. and Brahemi, G. (2008) Protein-protein interactions as targets for small molecule therapeutics. Expert Reviews in Molecular Medicine 10, 1-14CrossRefGoogle ScholarPubMed