The strategy of initial conservative management and delayed hormone therapy is a reasonable choice for some men with grade 1 or 2 clinically localized prostate cancer, particularly for those who have an average life expectancy of 10 years or less. New treatment strategies are needed for men with grade 3 prostate cancer.
TRPM-2, not normally expressed in the rat ventral prostate, has been identified as an important genetic marker of castration-induced apoptotic cell death. It is not known whether other agents capable of causing growth inhibition of the rat ventral prostate also induce TRPM-2 expression. To investigate this further, 270 mature Sprague-Dawley rats were randomized into one of six groups: control, castration, diethylstilbestrol (DES), flutamide, MK-906 (finasteride), or coumarin. Five rats per group were sacrificed on days 1, 3, 5, 7, 10, and 21. Serum testosterone, body weights, and prostate weights were determined at each time point. The ventral prostate was removed and cellular RNA extracted. Northern blot analysis using cDNA probes for TRPM-2 and gamma-actin were performed at each time point. Only DES significantly decreased rat weights. DES and castration reduced serum testosterone to undetectable levels by the next day. Flutamide caused a 3.0- to 4.5-fold increase in serum testosterone above control. Coumarin and MK-906 did not affect serum testosterone levels. DES and castration reduced prostate weights to 20% and 6% of control, respectively, while inducing TRPM-2 expression to a maximum on day 5 of the experiment. DES induced TRPM-2 expression over a longer duration than did castration, suggesting that more than just the decrease of serum testosterone to castrate levels plays a role in the expression of TRPM-2. MK-906, coumarin, and flutamide reduced prostatic weights to a lesser extent (50%, 63%, 71% of control, respectively), but these agents did not induce TRPM-2 expression at any time during the experiment. TRPM-2 expression in the rat ventral prostate does not correlate simply with catabolic effects on the prostate.
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