Androgen ablation therapies are effective in controlling prostate cancer. Although most cancers relapse and progress despite androgen ablation, some patients experience antiandrogen withdrawal syndrome, in which those treated with antiandrogen show clinical improvement when antiandrogen is discontinued. Although the androgen receptor (AR) is suggested to play an important role in prostate cancer progression even after the androgen ablation, limited tissue availability for molecular studies and small numbers of human prostate cancer cell lines have restricted prostate cancer research. Here, we describe KUCaP, a novel serially transplantable human prostate cancer xenograft model. We established KUCaP from liver metastatic tissue of a patient treated with antiandrogen bicalutamide. KUCaP expressed the AR with a point mutation at amino acid 741 (tryptophan to cysteine; W741C) in the ligand-binding domain. This mutation was also present in cancerous tissue used for generation of KUCaP. Although the growth of KUCaP in male mice was androgen dependent, bicalutamide aberrantly promoted the growth and prostate-specific antigen production of KUCaP. For the first time, we show the agonistic effect of bicalutamide to a xenograft with clinically induced AR mutation. This bicalutamide-responsive mutant AR will serve in the development of new therapies for androgen ablation-resistant prostate cancers. (Cancer Res 2005; 65(21): 9611-6)

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men who under radical prostatectomy. The correlation between the expression of Akt and p-Akt, and their relationship to primary Gleason grade, AR expression and Ki-67 LI was investigated. RESULTSThe expression of Akt and p-Akt were positively related to primary Gleason grade (Fisher's exact test, P = 0.002 and P = 0.032, respectively). Both AR-staining score and Ki67 LI were were positively related to the expression of Akt (both P < 0.001) and p-Akt ( P < 0.001 and P = 0.008, respectively). There was a significant positive correlation between the expression of Akt and p-Akt (Spearman's correlation, r = 0.644, P < 0.001). CONCLUSIONSIncreased expression of both Akt and p-Akt were associated with higher tumour grade as well as a higher AR-staining score and Ki67 LI. These data indicate that Akt and p-Akt might be molecular markers for detecting malignant biological features of prostate cancer in the Japanese population.

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