A Novel Approach to the Elucidation of the Mechanism of Development of Androgen-Independent Growth of Prostate Cancer.
Annual rept. 1 Jul 98-30 Jun 99
NORTH CAROLINA UNIV AT CHAPEL HILL
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The human CaP xenograft, CWR22, retains the biological characteristics exhibited by most human CaPs, including regression following castration and recurrence several months after the removal of androgen recurrent CWR22. Two subtracted cDNA library pools were constructed from 20 day castrate CWR22 non-proliferating tumor in androgen absence and recurrent CWR22 proliferative tumor in androgen absence and were compared to identify genes whose gain of function gene expression elevated in recurrent CWR22 relative to 20 day castrate CWR22 or loss of suppression gene expression elevated in 20 day castrate CWR22 relative to recurrent CWR22 are associated with the onset of cellular proliferation. The first 9 clones identified by screening slot blots included 8 that were upregulated and one that was suppressed in recurrent CWR22 among the first 96 clones examined from the forward subtracted library. Candidate genes will be associated with the onset of androgen-independent cellular proliferation in CWR22 cellular proliferation begins between 105 and 115 days after castration as determined using image analysis before characterization in a large number of prostatectomy specimens of androgen-dependent and independent CaP and then in an invaluable set of serial biopsies of advanced human prostate cancer obtained before and after castration.
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