Novel Coactivators for Androgen Receptor
Abstract
Contact between the extracellular matrix and specific cell surface proteins occurs at specialized structures termed focal adhesions, which include several signal transduction molecules such as focal adhesion kinase (FAK). FAK is elevated in metastatic prostate cancer (PC) and preferentially associated with tyrosine-phosphorylated paxillin. In addition to its localization to focal adhesions, paxillin is also present within nuclei of cultured PC cell lines and human prostate tissue. Furthermore, paxillin functions as a coactivator for androgen receptor (AR) and directly interacts with AR both in vitro and in PC cell lines. An interaction between paxillin and AR was detected in soluble extracts and membrane fractions from PC cell lines. Thus, paxillin, a protein that responds to the metastatic state of PC cells, can directly influence AR transactivation. siRNA-mediated ablation of paxillin in PC cell lines confirmed the importance of paxillin for maximal AR transactivation. Affects of paxillin and related family members (e.g. Hic-5/ARA55) on AR transactivation in prostate tissue may also be influenced by compartment-specific expression as paxillin was detected primarily in epithelial cells in normal and cancerous prostate tissue while Hic-5/ARA55 expression was limited to stromal cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA438207
Entities
People
- Donald B. Defranco
Organizations
- University of Pittsburgh