The Role of Stat3 in Breast Cancer Tumorigenesis
Abstract
Signal Transducers and Activators of Transcription (STATs) are a family of transcription factors which are normally "inactive" within the cytoplasm of cells and upon tyrosine phosphorylation become "activated'1 which leads to the dimerization of two Stat molecules. Dimerized Stats are translocated into the nucleus where they bind DNA and activate transcription. Stat dimers are dephosphorylated within the nucleus and transported back to the cytoplasm (1). Virtually all growth factor receptors, cytokines, and tyrosine kinases lead to the phosphorylation of one or more Stat proteins. In "normal" cells this activation is transient, while in an ever growing number of primary tumors and cancer derived cell lines Stat proteins (in particular Stat3) are constitutively activated (1, 2). A causal association between activated Stat3 and cellular transformation or oncogenesis has been made in a large number of cancer derived cell lines. Specifically, removal of Stat3 by the introduction of a dominant negative Stat3 molecule or anti-sense molecule leads to a reversal of the transformed phenotype, induction of apoptosis , decreased angiogenesis or growth arrest (Figure 1).
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA409607
Entities
People
- Jacqueline F. Bromberg
Organizations
- Memorial Sloan Kettering Cancer Center