Amplification of urokinase gene in prostate cancer

Prostate cancer is the most common male malignancy in the United States as well as in many European countries, It is curable as long as it is localize d, but the invasion of prostate cancer and formation of metastasis turn it into a life-threatening disease. Urokinase-type plasminogen activator (uPA) is believed to play a key role in tissue degradation and cell migration un der various normal and pathological conditions, including cancer invasion a nd metastasis, Increased expression of uPA has been reported in various mal ignancies including prostate cancer. However, the mechanisms of the overexp ression have remained poorly understood. Here, we report increased copy num ber of uPA gene in 3 of 13 hormone-refractory prostate carcinomas, includin g 1 high-level amplification. Realtime quantitative reverse transcription-P CR showed that the increased expression of uPA coincided with the amplifica tion of the gene in these tumors, Matrigel invasion assay showed that prost ate cancer cell line PC-3, containing amplification of the uPA gene, was mo re sensitive to the urokinase inhibitor, amiloride, than DU145 or LNCaP cel l lines, which do not have the amplification. The findings suggest that one of the mechanisms underlying the overexpression of the uPA is the amplific ation of the gene, which is associated with the increased invasive potentia l of the cells.