Molecular Mechanisms of Hormone-Refractory Prostate Cancer
Abstract
The concept to be tested here is that the various tyrosine kinase pathways known to contribute to antiandrogen 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. Indeed, our results support a role for Crk in androgen resistance signaling pathways. At the same time, our studies demonstrate that a docking molecule other than Cas, but possessing a similar molecular weight, functions to couple Crk to the upstream tyrosine kinases. This molecule was identified as the docking protein CbI by using mass spectrometry techniques. In sum, we have established a correlation between androgen independence and Cbl/Crk signaling, as proposed in our application. Our next objective is to continue these promising studies, and examine whether activation of Ork 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, 2006
- Accession Number
- ADA452514
Entities
People
- Kristiina Vuori
Organizations
- Sanford Burnham Prebys Medical Discovery Institute