scholarly journals A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene

Blood ◽  
1995 ◽  
Vol 86 (2) ◽  
pp. 624-635 ◽  
Author(s):  
E Soravia ◽  
A Grebe ◽  
P De Luca ◽  
K Helin ◽  
TT Suh ◽  
...  

The urokinase-type plasminogen activator receptor (uPAR) focuses at the cell surface the activation of pro-uPA and, hence, the formation of plasmin, thus enhancing directional extracellular proteolysis. To characterize the transcriptional regulatory mechanisms that control receptor expression, we have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes and contains relatively GC-rich proximal sequences. A subregion of this sequence, highly conserved between human and murine genes, contains most of the promoter activity and is specifically bound by HeLa nuclear proteins, one of which belongs to the SP1 class.

Gut ◽  
1998 ◽  
Vol 43 (6) ◽  
pp. 798-805 ◽  
Author(s):  
S Suzuki ◽  
Y Hayashi ◽  
Y Wang ◽  
T Nakamura ◽  
Y Morita ◽  
...  

Background—The urokinase type plasminogen activator receptor (uPAR) may play a critical role in cancer invasion and metastasis.Aims—To study the involvement of uPAR in colorectal carcinogenesis.Methods—The cellular expression and localisation of uPAR were investigated in colorectal adenomas and invasive carcinomas by in situ hybridisation, immunohistochemistry, and northern and western blot analyses.Results—uPAR mRNA expression was found mainly in the cytoplasm of dysplastic epithelial cells of 30% of adenomas with mild (19%), moderate (21%), and severe (47%) dysplasia, and in that of carcinomatous cells of 85% of invasive carcinomas: Dukes’ stages A (72%), B (93%), and C (91%). Some stromal cells in the adjacent neoplastic epithelium were faintly positive. Immunoreactivity for uPAR was detected in dysplastic epithelial cells of 14% of adenomas and in carcinomatous cells of 49% of invasive carcinomas. uPAR mRNA and protein concentrations were significantly higher in severe than in mild or moderate dysplasia (p<0.05); they were notably higher in Dukes’ stage A than in severe dysplasia (p<0.05), and significantly higher in Dukes’ stage B than in stage A (p<0.05), but those in stage B were not different from those in stage C or in metastatic colorectal carcinomas of the liver.Conclusions—Colorectal adenoma uPAR, expressed essentially in dysplastic epithelial cells, was upregulated with increasing severity of atypia, and increased notably during the critical transition from severe dysplasic adenoma to invasive carcinoma. These findings implicate uPAR expression in the invasive and metastatic processes of colorectal cancer.


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