Transcriptional and posttranscriptional activation of urokinase plasminogen activator gene expression in metastatic tumor cells

Henderson, B. R., Tansey, W. P., Phillips, S. M., Ramshaw, I. A., Kefford, R. F. (May 1992) Transcriptional and posttranscriptional activation of urokinase plasminogen activator gene expression in metastatic tumor cells. Cancer Res, 52 (9). pp. 2489-96. ISSN 0008-5472 (Print)0008-5472 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/1568219

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: 9,10-Dimethyl-1,2-benzanthracene Amino Acid Sequence Animals DNA/*chemistry Down-Regulation Enzyme Activation/genetics Female Gene Expression Regulation, Enzymologic/*genetics Gene Expression Regulation, Neoplastic/*genetics Mammary Neoplasms, Experimental/*enzymology/genetics Molecular Sequence Data RNA, Messenger/analysis Rats Rats, Inbred F344 Transcription, Genetic/*genetics Transcriptional Activation Urokinase-Type Plasminogen Activator/biosynthesis/*genetics
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
diseases & disorders > cancer > metastasis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > post transcriptional modification
CSHL Authors:
Communities: CSHL labs > Tansey lab
Depositing User: Matt Covey
Date: 1 May 1992
Date Deposited: 01 Oct 2015 19:19
Last Modified: 01 Oct 2015 19:19
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31776

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving