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Urokinase-type plasminogen activator gene regulation by polyomavirus middle-T antigen

Item Type:Article
Title:Urokinase-type plasminogen activator gene regulation by polyomavirus middle-T antigen
Creators Name:Besser, D. and Urich, M. and Sakaue, M. and Messerschmitt, A. and Ballmer-Hofer, K. and Nagamine, Y.
Abstract:Expression of polyomavirus middle-T antigen (middle-T) is involved in the formation of various tumors in vivo, e.g. hemangiomas and mammary gland tumors. Several genes have been shown to be activated in middle-T-expressing cells, but the underlying mechanisms have only been partially elucidated. Among the genes regulated by middle-T, the urokinase-type plasminogen activator (uPA) gene seems to be of primary importance for the development of the transformed phenotype. We have found that the uPA gene is highly expressed in eEnd2 cells derived from a hemangioma expressing middle-T. NIH3T3 cells show negligible levels of uPA mRNA but its expression was highly induced by infecting with a middle-T-expressing retrovirus. Middle-T did not affect uPA mRNA stability. Transient cotransfection experiments using a uPA-receptor gene construct and a middle-T expression vector showed that high uPA mRNA levels are due to increased uPA promoter activity. Analyses of various signaling molecules by transient cotransfection assays and in vitro kinase assays established that a signaling pathway involving c-Src, SOS, Ras, Raf-1 and ERK is activated by middle-T in NIH3T3 cells, resulting in the activation of the uPA gene promoter via PEA3/AP1 elements. In contrast, in eEND2 cells uPA gene induction is only partially dependent on this pathway, suggesting the involvement of additional signaling molecules in endothelial cells.
Keywords:3T3 Cells, Polyomavirus Transforming Antigens, Base Sequence, Calcium-Calmodulin-Dependent Protein Kinases, Recombinant DNA, Enzymologic Gene Expression Regulation, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Genetic Promoter Regions, Proto-Oncogene Proteins, Messenger RNA, , Signal Transduction, Transcription Factor AP-1, Transcriptional Activation, Urokinase-Type Plasminogen Activator, Animals, Mice
Publisher:Nature Publishing Group
Page Range:2383-2391
Date:7 December 1995
PubMed:View item in PubMed

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