This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Henderson, B. R. Articles by Kefford, R. F. Search for Related Content PubMed PubMed Citation Articles by Henderson, B. R. Articles by Kefford, R. F.

Transcriptional and Posttranscriptional Activation of Urokinase Plasminogen Activator Gene Expression in Metastatic Tumor Cells¹

Medical Oncology Unit, Department of Medicine, University of Sydney, Westmead Hospital, Westmead, New South Wales 2145 [B. R. H., W. P. T., R. F. K.] and Division of Cell Biology, John Curtin School of Medical Research, Australian National University, P. O. Box 334, Canberra, A.C.T. 2601 [S. M. P., I. A. R.], Australia

Urokinase plasminogen activator (uPA) is a serine protease which has frequently been implicated in the process of tumor cell invasion and metastasis. The degree of expression and mode(s) of regulation of the uPA gene in metastatic compared with nonmetastatic tumor cells have not yet been addressed. We have cloned and sequenced a full-length rat uPA complementary DNA and utilized Northern blot analysis to report that the uPA gene is expressed at levels 3.5- to 70-fold higher in metastatic cell lines than in nonmetastatic cell lines derived from two independent rat mammary adenocarcinomas. Nuclear run-on assays and RNA half-life estimations indicated that metastatic MAT 13762 rat mammary adenocarcinoma cells expressed 3.5-fold higher levels of uPA RNA than a nonmetastatic derivative (J-clone), due to a combined increase in uPA gene transcription and cytoplasmic RNA stability. By contrast, uPA RNA (and enzyme) levels were elevated by up to 70-fold in metastatic clones of dimethylbenz(a)anthracene-induced rat mammary adenocarcinoma (DMBA-8) due to predominantly posttranscriptional mechanisms. Moreover, treatment of nonmetastatic DMBA-8 cell lines with protein synthesis inhibitors led to an increase in nuclear and cytoplasmic uPA RNA levels, without altering the rate of uPA gene transcription. These results suggest that in addition to gene transcription, posttranscriptional events localized in the nucleus and cytoplasm are key determinants of uPA gene activation in rat mammary adenocarcinomas.

¹ This work was supported in part by a grant from the University of Sydney Cancer Research Fund.

² To whom requests for reprints should be addressed. Recipient of a Research Fellowship from the University of Sydney Medical Foundation.

Received 6/21/91. Accepted 2/26/92.

This article has been cited by other articles:

				S. Shetty and S. Idell Post-transcriptional Regulation of Urokinase mRNA. IDENTIFICATION OF A NOVEL UROKINASE mRNA-BINDING PROTEIN IN HUMAN LUNG EPITHELIAL CELLS IN VITRO J. Biol. Chem., April 28, 2000; 275(18): 13771 - 13779. [Abstract] [Full Text] [PDF]

				M. Schloesser, S. Zeerleder, G. Lutze, W.-M. Halbmayer, S. Hofferbert, B. Hinney, H. Koestering, B. Lammle, G. Pindur, K. Thies, et al. Mutations in the Human Factor XII Gene Blood, November 15, 1997; 90(10): 3967 - 3977. [Abstract] [Full Text] [PDF]