Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1992-5-26
pubmed:databankReference
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2489-96
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:1568219-9,10-Dimethyl-1,2-benzanthracene, pubmed-meshheading:1568219-Amino Acid Sequence, pubmed-meshheading:1568219-Animals, pubmed-meshheading:1568219-DNA, pubmed-meshheading:1568219-Down-Regulation, pubmed-meshheading:1568219-Enzyme Activation, pubmed-meshheading:1568219-Female, pubmed-meshheading:1568219-Gene Expression Regulation, Enzymologic, pubmed-meshheading:1568219-Gene Expression Regulation, Neoplastic, pubmed-meshheading:1568219-Mammary Neoplasms, Experimental, pubmed-meshheading:1568219-Molecular Sequence Data, pubmed-meshheading:1568219-RNA, Messenger, pubmed-meshheading:1568219-Rats, pubmed-meshheading:1568219-Rats, Inbred F344, pubmed-meshheading:1568219-Transcription, Genetic, pubmed-meshheading:1568219-Transcriptional Activation, pubmed-meshheading:1568219-Urokinase-Type Plasminogen Activator
pubmed:year
1992
pubmed:articleTitle
Transcriptional and posttranscriptional activation of urokinase plasminogen activator gene expression in metastatic tumor cells.
pubmed:affiliation
Department of Medicine, University of Sydney, Westmead Hospital, New South Wales, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't