Prostate cancer is one of the malignant tumors which exhibit resistance to anticancer drugs, at least in part due to enhanced antiapoptotic mechanisms. Therefore, the understanding of such mechanisms should improve the design of chemotherapy against prostate cancer. Galectin-3 (Gal-3), a multifunctional oncogenic protein involved in the regulation of tumor proliferation, angiogenesis, and apoptosis has shown antiapoptotic effects in certain cell types. Here, we show that the expression of exogenous Gal-3 in human prostate cancer LNCaP cells, which do not express Gal-3 constitutively, inhibits anticancer drug-induced apoptosis by stabilizing the mitochondria. Thus, Gal-3-negative cells showed 66.31% apoptosis after treatment with 50 Mmol/L cis-diammine-dichloroplatinum for 48 hours, whereas two clones of Gal-3-expressing cells show only 2.92% and 1.42% apoptotic cells. Similarly, Gal-3-negative cells showed 43.8% apoptosis after treatment with 300 Mmol/L etoposide for 48 hours, whereas only 15.38% and 14.51% of Gal-3-expressing LNCaP cells were apoptotic. The expression of Gal-3 stimulated the phosphorylation of Ser 112 of Bcl-2-associated death (Bad) protein and down-regulated Bad expression after treatment with cis-diammine-dichloroplatinum. Gal-3 also inhibited mitochondrial depolarization and damage after translocation from the nuclei to the cytoplasm, resulting in inhibition of cytochrome c release and caspase-3 activation. These findings indicate that Gal-3 inhibits anticancer drug-induced apoptosis through regulation of Bad protein and suppression of the mitochondrial apoptosis pathway. Therefore, targeting Gal-3 could improve the efficacy of anticancer drug chemotherapy in prostate cancer. (Cancer Res 2006; 66(6): 3114-9)

clinicopathological factors. Immunohistochemical expression was examined using confocal laser scanning lightmicroscopy. RESULTSPSCA was overexpressed in all RCC cell lines. PSCA mRNA levels were significantly higher in CC-RCC than in normal kidney tissue samples ( P < 0.001), in G2-G3 than in G1 tumours ( P = 0.028), and in advanced disease (T3-T4) than in organ-confined (T1-T2) tumours ( P = 0.016). There was significantly higher PSCA mRNA expression in patients with M1 than in those with M0 disease ( P = 0.029). Patients in whom the lesions had high PSCA expression levels had a significantly worse prognosis than those with low PSCA expression levels ( P = 0.044). Using immunohistochemical analysis there was markedly greater PSCA expression in CC-RCC than in normal kidney, and in advanceddisease high-grade tumours than in organconfined low-grade tumours. CONCLUSIONSA significant correlation was detected in the gene expression level of PSCA with histological grade, clinicopathological stage and prognosis in CC-RCC. Our data indicate that PSCA is associated with carcinogenesis and progression of CC-RCC.

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OBJECTIVES To evaluate the relationship between prostate stem cell antigen (PSCA) expression level in transitional cell carcinoma (TCC) of the urinary bladder and various clinicopathological features, including stage and grade; and to determine whether PSCA mRNA expression predicts disease recurrence in superficial (not muscle‐invasive) TCC of the bladder. PATIENTS AND METHODS Real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) was performed on 97 TCC tissue samples and in 36 samples of normal bladder urothelium; the findings were analysed in relation to clinicopathological factors. Immunohistochemical expression was examined using light and confocal immunofluorescence microscopy to validate the RT‐PCR data. RESULTS Twenty‐seven patients developed disease recurrence, while the remaining 22 had no evidence of recurrence of superficial TCC of the bladder. There was significantly higher PSCA mRNA expression in TCC than in normal urothelium samples (P = 0.008). Superficial (TaT1) tumours had significantly higher PSCA expression than muscle‐invasive (≥ pT2) tumours (P < 0.001). There was no significant difference between patients with G1–2 tumours and those with G3 tumours (P = 0.109). Immunohistochemical analysis showed markedly greater PSCA expression in superficial than invasive TCC. Notably, from a multivariate analysis, the expression level of PSCA was an independent predictor of disease recurrence in superficial TCC (P = 0.012). CONCLUSIONS These findings suggest that the PSCA expression level measured by real‐time RT‐PCR could be a valuable prognostic marker for tumour recurrence in superficial TCC of the bladder.

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