Characterization of Putative Homeostatic Molecules in Prostate Development and Androgen-Independent Prostate Cancer
Abstract
It is believed that androgen independent (A') prostate cancer (PCa) cells behave like the basal cells in prostate gland with malignant phenotype. Basal cells represent a stem cell population of prostate. Therefore, we believe that a genetic imbalance for controlling growth and/or differentiation in basal cell will result in the onset of AIPCa. Our previous studies discover a novel protein- DOC-2 that are associated with normal basal cell of prostate and are often absents in prostate cancer. Most importantly, we identified a novel RAS-GTPase activating protein (i.e., DIP 1/2) interacting with DOC-2 protein. In this project, we have studied the regulation of DIP 1/2 in prostate cancer cells and signal transduction of DOC-2/DIP 1/2 complex during cell differentiation of prostatic epithelium. In summary, we demonstrated that epigenetic control such as DNA methylation and histone acetylation plays an important role in modulating DIP1/2 gene expression in AIPCa. The re-expression of DIP1/2 was able to suppress the growth of PCa cells. Using a three-dimension in vitro tissue culture system, the elevated DIP 1/2 protein and several other genes (such as P-cadherin, prostate-derived factor) correlated with the cell polarization of basal epithelium. Furthermore, DIP 1/2-expressing cells can form glandular tissue in vivo. Thus, DIP 1/2 is a critical factor involved in cell differentiation of prostatic epithelium.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA418678
Entities
People
- Jer-Tsong Hsieh
Organizations
- University of Texas at Dallas