A Novel Approach to the Elucidation of the Mechanism of Development of Androgen-Independent Growth of Prostate Cancer
Abstract
The human prostate cancer (CaP) xenograft, CWR22 regresses after castration and recurs several months after removal of androgen (recurrent CWR22). Two subtracted cDNA library pools constructed from 20-day castrate CWR22 (non-proliferating tumor in androgen absence) and recurrent CWR22 (proliferating tumor in androgen absence) were compared to identify genes whose gain of function (gene expression elevated in recurrent CWR22 vs. 20-day castrate CWR22) or loss of suppression (gene expression elevated in 20-day castrate CWR22 vs. recurrent CWR22) were associated with onset of cellular proliferation. Of 1057 clones examined, ii candidate genes were identified, all of which were upregulated in recurrent CWR22 Northern analysis confirmed differential expression of 9 genes. Western analysis revealed an association between tomoregulin, elongation factor alpha and thioredoxin reductase and the onset of androgen-independent growth. Immunohistochemistry revealed expression of tomoregulin in small foci of proliferating cells first recognized on day 90 after castration. Candidate genes will be characterized in a large number of prostatectomy specimens of androgen-dependent and independent CaP and then in an invaluable set of serial biopsies obtained before and after castration of men with advanced CaP. One of these genes may represent an appropriate target to prevent, delay or treat androgen-independent growth of CaP.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2001
- Accession Number
- ADB268296
Entities
People
- James L Mohler
Organizations
- University of North Carolina at Chapel Hill