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Clinical cancer research, 2004-01, Vol.10 (2), p.440-448
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2004
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Purpose. Prostate cancer that recurs during androgen deprivation therapy is referred to as androgen-independent. High levels of expression
of androgen receptor and androgen receptor-regulated genes in recurrent prostate cancer suggest a role for androgen receptor
and its ligands in prostate cancer recurrence.
Experimental Design. Recurrent prostate cancer specimens from 22 men whose prostate cancer recurred locally during androgen deprivation therapy
and benign prostate specimens from 48 men who had received no prior treatment were studied. Androgen receptor expression was
measured using monoclonal antibody and automated digital video image analysis. Tissue androgens were measured using radioimmunoassay.
Results. Epithelial nuclei androgen receptor immunostaining in recurrent prostate cancer (mean optical density, 0.284 ± SD 0.115 and
percentage positive nuclei, 83.7 ± 11.6) was similar to benign prostate (mean optical density, 0.315 ± 0.044 and percentage
positive nuclei, 77.3 ± 13.0). Tissue levels of testosterone were similar in recurrent prostate cancer (2.78 ± 2.34 pmol/g
tissue) and benign prostate (3.26 ± 2.66 pmol/g tissue). Tissue levels of dihydrotestosterone, dehydroepiandrosterone, and
androstenedione were lower (Wilcoxon, P = 0.0000068, 0.00093, and 0.0089, respectively) in recurrent prostate cancer than in benign prostate, and mean dihydrotestosterone
levels, although reduced, remained 1.45 n m . Androgen receptor activation in recurrent prostate cancer was suggested by the androgen-regulated gene product, prostate-specific
antigen, at 8.80 ± 10.80 nmol/g tissue.
Conclusions. Testosterone and dihydrotestosterone occur in recurrent prostate cancer tissue at levels sufficient to activate androgen
receptor. Novel therapies for recurrent prostate cancer should target androgen receptor directly and prevent the formation
of androgens within prostate cancer tissue.