McGarvey T W, Kariko K, Barnathan E S, Thomas J, Malkowicz S B
Department of Surgery, Division of Urology, University of Pennsylvania Medical Center, Veterans Administration Medical Center, Department of Cardiology, Philadelphia, PA 19104, USA.
Int J Oncol. 1998 Jan;12(1):175-80. doi: 10.3892/ijo.12.1.175.
Tumor invasion and metastasis is mediated in part by proteolytic enzymes including urokinase plasminogen activator (uPA). The object of this study was to quantitate the molecular expression of urokinase plasminogen activator-related components in human superficial and invasive transitional cell carcinoma tumors (TCC), as well as parental and invasive variant TCC cell lines. We examined 15 invasive and 14 superficial TCC tumors (from a total of 29 patients) and six bladder carcinoma cell 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 increase in uPA expression in invasive lesions compared to superficial tumors (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, there 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 superficial 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 chamber demonstrated higher levels of uPA, uPA receptor and PAI-1 than parental cells (p < 0.05). These data from the human tumor specimens suggest that increased uPA and uPAr expression may be component of the invasive phenotype of TCC lesions.
肿瘤侵袭和转移部分是由包括尿激酶型纤溶酶原激活剂（uPA）在内的蛋白水解酶介导的。本研究的目的是定量检测尿激酶型纤溶酶原激活剂相关成分在人浅表性和浸润性移行细胞癌肿瘤（TCC）以及亲本和浸润性变异TCC细胞系中的分子表达。我们通过定量逆转录聚合酶链反应（RT-PCR）检测了15例浸润性和14例浅表性TCC肿瘤（共29例患者）以及6种膀胱癌细胞系中uPA、uPA受体和uPA抑制剂-1的稳态mRNA水平，并将其标准化为L7核糖体转录本（一个管家基因）。转录水平以与L7管家转录本的比值表示。与浅表肿瘤相比，浸润性病变中uPA表达增加了三倍（p < 0.003）。此外，浸润性TCC中uPA受体转录本也相应增加了2.7倍（p < 0.008）。然而，浸润性和浅表性肿瘤之间PAI-1 mRNA的稳态水平没有显著差异。尿激酶相关基因的转录水平在正常黏膜和浅表肿瘤之间相似。培养的细胞（亲本和浸润性变异细胞）总体上表达较高水平的三种uPA相关基因。通过Boyden小室连续传代选择的浸润性TCC细胞显示出比亲本细胞更高水平的uPA、uPA受体和PAI-1（p < 0.05）。来自人类肿瘤标本的数据表明，uPA和uPAr表达增加可能是TCC病变浸润表型的组成部分。
