Regulation of human tissue-type plasminogen activator gene transcription by epidermal growth factor and 3′,5′-Cyclic adenosine monophosphate

Robert L. Medcalf, Wolf Dieter Schleuning

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Abstract

Epidermal growth factor (EGF) induces tissue-type plasminogen activator (t-PA) biosynthesis in HeLa cells. Based on nuclear run-on transcription assays, t-PA biosynthesis is modulated by EGF on the level of gene transcription. The effect of EGF is slow, requiring 4-8 h to induce t-PA gene transcription and up to 24 h to induce t-PA mRNA and antigen secretion. An additive response is observed when cells are treated with both phorbol 12-myristate 13-acetate and EGF, suggesting that the two pathways converge and act independently to implement their respective effects. cAMP has previously been shown to potentiate phorbol 12-myristate 13-acetate-mediated induction of t-PA biosynthesis in HeLa cells and in human endothelial cells. Akin to this observation, cAMP also potentiates the EGF-mediated increase in t-PA mRNA. Maximal levels of t-PA mRNA is seen in the presence of all three agonists. The regulation of t-PA by EGF alone and in the presence of either PMA or cAMP is consistent with a role of t-PA during growth and development, and further indicates a functional interplay between protein kinase C-, tyrosine kinase, -and cAMP-dependent signal transduction pathways during regulation of t-PA gene expression.

Original languageEnglish
Pages (from-to)1773-1779
Number of pages7
JournalMolecular Endocrinology
Volume5
Issue number12
DOIs
Publication statusPublished - 1 Jan 1991
Externally publishedYes

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