Tyrosine Kinase Display of Prostate Cancer Cells
Abstract
In this proposal, we present an innovative approach, tyrosine kinase display, to rapidly identify tyrosine kinases differentially expressed in prostate carcinomas. Our hypothesis is that tyrosine kinases play central roles to the growth and progression of prostate carcinomas. Knowledge of tissue- or stage-specific tyrosine kinases could potentially provide better prognostic markers and intervention strategies. The innovative PCR-based approach developed here requires only restriction digestion and gel electrophoresis, and allows all or nearly all expressed tyrosine kinases to be directly "read" from the gel. It is rapid, quantitative, and insensitive to RNA degradation and requires minimal amounts of RNA. When fully developed, it is expected to have wide-applications in both basic and clinical settings. In the past two and half years (May, 1999 to Sept. 2001), we have made significant progress, notably 1). We have established comprehensive tyrosine kinase profiles for all six widely used prostate cancer cell lines and three LNCaP androgen-independent variant cell lines, as well as those of immortalized prostate epithelial cells and the normal primary cultures of prostate stromal and epithelial cells; 2). We have identified several kinases differentially expressed in prostate cancer cells, in androgen-dependent as well as -independent cells. These are potential prognostic markers and intervention targets; 3). We have identified a new kinase whose expression is induced by DHT and which may mediate signals channelled by androgen receptor. Modulation of this kinase activity may restore androgen sensitivity or block androgen independent growth; and 4). We have validated the important biological roles of the Etk, the first novel tyrosine kinase uncovered by tyrosine kinase profile, in prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADB282106
Entities
People
- Kung Hsing-jien
Organizations
- University of California