Molecular Mechanisms of Hormone-Refractory Prostate Cancer
Abstract
The concept to be tested herein is that the various tyrosine kinase pathways known to contribute to anti-androgen resistance likely converge on a common signaling molecule that integrates the upstream signaling input and leads to androgen receptor activation in an androgen-independent manner. Identification of the signal-integrating molecule(s) would provide a valuable therapeutic target for prostate cancer. We hypothesized that the intracellular docking protein Cas, complexed with the adapter protein Crk, could have such a signal-integrating role. Our studies performed so far support a role for Crk in androgen resistance signaling pathways. At the same time, our studies suggest that a docking molecule other than Cas, but possessing a similar molecular weight, functions to couple Crk to the upstream tyrosine kinases. Thus, we have established a correlation between androgen independence and Ork signaling, as proposed in the aim 1 of our application. Our next objective is to molecularly identify the signal integrating docking molecule, and then proceed to aim 2 and examine whether activation of Crk signaling is causal to androgen independence in prostate cancer cells in vitro. Our long-term objective is to utilize the obtained information to develop specific and sensitive tools for diagnosis and therapeutics of anti-androgen resistance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2005
- Accession Number
- ADA435559
Entities
People
- Kristiina Vuori
Organizations
- Sanford Burnham Prebys Medical Discovery Institute