期刊
EXPERT REVIEWS IN MOLECULAR MEDICINE
卷 11, 期 -, 页码 -出版社
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S1462399409001033
关键词
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资金
- NIH [R01 CA113795]
- Susan G. Komen for the Cure Program
- Flight Attendant Medical Research Institute
- Hansen Foundation
- Johns Hopkins Breast Cancer Program
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/EBP beta 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/EBPb 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/EBP beta isoforms in breast cancer is discussed and emphasis is placed on their interactions with receptor tyrosine kinases.
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