CCAAT/enhancer-binding protein beta: its role in breast cancer and associations with receptor tyrosine kinases.
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/EBPbeta 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/EBPbeta 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/EBPbeta isoforms in breast cancer is discussed and emphasis is placed on their interactions with receptor tyrosine kinases.
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Bunting-Blaustein Cancer Research Building, 1650 Orleans St, Baltimore, MD 21231-1000, USA. zahnoci@jhmi.edu
Cynthia A
CA
Zahnow
D001943:Breast Neoplasms / Q000209:etiology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D011499:Protein Processing, Post-Translational; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*
D022762:CCAAT-Enhancer-Binding Proteins; D020794:Receptor Protein-Tyrosine Kinases