THE EXPRESSION OF UROKINASE-RELATED GENES IN SUPERFICIAL AND INVASIVETRANSITIONAL-CELL CARCINOMA

Tumor invasion and metastasis is mediated in part by proteolytic enzym es including urokinase plasminogen activator (uPA). The object of this study was to quantitate the molecular expression of urokinase plasmin ogen activator-related components in human superficial and invasive tr ansitional cell carcinoma tumors (TCC), as well as parental and invasi ve variant TCC cell lines. We examined 15 invasive arid 14 superficial TCC tumors (from a total of 29 patients) and six bladder carcinoma ce ll lines for the steady state mRNA levels of uPA, the uPA receptor and uPA inhibitor-1 by quantitative RT-PCR normalized to the L7 ribosomal transcript (a housekeeping gene). Transcript levels were expressed in a ratio to the L7 housekeeping transcript. There was a three fold inc rease in uPA expression in invasive lesions compared to superficial tu mors (p<0.003). In addition, there was a concordant 2.7 fold increase in the uPA receptor transcript in invasive TCC (p<0.008). However, the re was no significant difference in the steady state levels of the PAI -1 mRNA between invasive and superficial tumors. Transcript levels for the urokinase-related genes were similar between normal mucosa and su perficial tumors. Cultured cells (parental and invasive variants) were found to express higher levels of the three uPA-related genes overall . Invasive TCC cells selected by serial passage through a Boyden chamb er demonstrated higher levels of uPA, uPA receptor and PAI-1 than pare ntal cells (p<0.05). These data from the human tumor specimens suggest that increased uPA and uPAr expression may be component of the invasi ve phenotype of TCC lesions.