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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-4-21
pubmed:abstractText
The urokinase-type plasminogen activator (uPA) and its cellular receptor (uPAR) are involved in the proteolytic cascade required for tumor cell dissemination and metastasis, and are highly expressed in many human tumors. We have recently reported that uPA, independently of its enzymatic activity, is able to increase the expression of its own receptor in uPAR-transfected kidney cells at a posttranscriptional level. In fact, uPA, upon binding uPAR, modulates the activity and/or the level of a mRNA-stabilizing factor that binds the coding region of uPAR-mRNA. We now investigate the relevance of uPA-mediated posttranscriptional regulation of uPAR expression in non small cell lung carcinoma (NSCLC), in which the up-regulation of uPAR expression is a prognostic marker. We show that uPA is able to increase uPAR expression, both at protein and mRNA levels, in primary cell cultures obtained from tumor and adjacent normal lung tissues of patients affected by NSCLC, thus suggesting that the enzyme can exert its effect in lung cells. We investigated the relationship among the levels of uPA, uPAR and uPAR-mRNA binding protein(s) in NSCLC. Lung tissue analysis of 35 NSCLC patients shows an increase of both uPA and uPAR in tumor tissues, as compared to adjacent normal tissues, in 27 patients (77%); 19 of these 27 patients also show a parallel increase of the level and/or binding activity of a cellular protein capable of binding the coding region of uPAR-mRNA. Therefore, in tumor tissues, a strong correlation is observed among these 3 parameters, uPA, uPAR and the level and/or the activity of a uPAR-mRNA binding protein. We then suggest that uPA regulates uPAR expression in NSCLC at a posttranscriptional level by increasing uPAR-stability through a cellular factor that binds the coding region of uPAR-mRNA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
353-60
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12704669-Blotting, Western, pubmed-meshheading:12704669-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:12704669-DNA, Complementary, pubmed-meshheading:12704669-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:12704669-Gene Expression Regulation, Enzymologic, pubmed-meshheading:12704669-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12704669-Humans, pubmed-meshheading:12704669-Lung Neoplasms, pubmed-meshheading:12704669-RNA, pubmed-meshheading:12704669-RNA, Messenger, pubmed-meshheading:12704669-RNA Processing, Post-Transcriptional, pubmed-meshheading:12704669-RNA-Binding Proteins, pubmed-meshheading:12704669-Receptors, Cell Surface, pubmed-meshheading:12704669-Receptors, Urokinase Plasminogen Activator, pubmed-meshheading:12704669-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12704669-Time Factors, pubmed-meshheading:12704669-Transcription, Genetic, pubmed-meshheading:12704669-Tumor Cells, Cultured, pubmed-meshheading:12704669-Up-Regulation, pubmed-meshheading:12704669-Urokinase-Type Plasminogen Activator
pubmed:year
2003
pubmed:articleTitle
Urokinase-mediated posttranscriptional regulation of urokinase-receptor expression in non small cell lung carcinoma.
pubmed:affiliation
Istituto di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't