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Regulation of urokinase‐type plasminogen activator expression in squamous‐cell carcinoma of the oral cavity
Author(s) -
Clayman G.,
Goepfert H.,
Boyd D. D.,
Wang S. W.,
Nicolson G. L.,
ElNaggar A.,
Mazar A.,
Henkin J.,
Blasi F.
Publication year - 1993
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910540113
Subject(s) - urokinase , urokinase receptor , plasminogen activator , cancer research , cell culture , microbiology and biotechnology , transfection , biology , cell , activator (genetics) , gene , endocrinology , biochemistry , genetics
We undertook a study to determine the role and regulation of expression of urokinase‐type plasminogen activator in squamous‐cell carcinoma of the oral cavity. The contribution of urokinase to the invasive process was clearly demonstrated in experiments in which in vitro invasion by a cultured squamous‐cell carcinoma cell line was substantially reduced by a monoclonal antibody directed at the catalytic site of urokinase. The conditioned medium from 2 invasive cell lines contained high levels of urokinase. Examination of resected tumors for urokinase revealed (a) localization of the antigen to the tumor cells and (b) higher levels of the plasminogen activator in tumor tissue than in adjacent non‐malignant tissue. These results suggested that elevated expression of urokinase is a common feature of this malignancy. The mRNA half‐lives of cell lines expressing high and low levels of urokinase were similar, indicating that elevated levels of mRNA for the plasminogen activator were not a consequence of a more stable transcript. No evidence of u‐PA gene amplification was obtained by Southern blotting of DNA derived from the cell lines expressing high urokinase levels. Transfection of squamous‐cell carcinoma cells, which express high levels of urokinase, with a construct bearing the chloram‐phenicol acetyl transferase gene driven by the full‐length (2345 bp) urokinase promoter indicated activation of the urokinase promoter in trans . In conclusion, our results suggest that transcriptional activation of the urokinase gene, in squamous‐cell carcinomas of the oral cavity, leads to elevated levels of urokinase mRNA/protein which, in turn, can promote the invasive phenotype.