Bedeutung des Endothelinsystems in der gynäkologischen Onkologie
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Forschungsarbeit aus dem Jahr 2007 im Fachbereich Medizin - Gynäkologie, Andrologie, Note: 1, Sprache: Deutsch, Abstract: Das Endothelinsystem, bestehend aus den drei Peptiden Endothelin (ET)-1, -2 und -3 sowie deren Rezeptoren, wird in zahlreichen menschlichen Zellen und Geweben exprimiert. Das biologisch aktiven ET-1 wird dabei durch das Endothelin-Converting Enzyme-1 (ECE-1) aus der inaktiven Vorstufe big-ET-1 gebildet. ET-1 hat sich als bedeutendes Peptid mit einer breiten Spanne biologischer Funktionen erwiesen, zu denen die Regulation von zellulärer Entwicklung, Proliferation, Apoptose und Angiogenese gehören. Dadurch ist das ET-1 von enormer physiologischer und pathophysiologischer Bedeutung. Während diese Effekte durch Bindung von ET-1 an den Endothelin-A-Rezeptor vermittelt werden, bewirkt Bindung von ET-1 an den Endothelin-B-Rezeptor eine Apoptosehemmung, reduzierte ECE-1-Expression sowie einen gesteigerten Abbau (Clearance) von ET-1. Die aktuelle Datenlage deutet darauf hin, dass das Endothelinsystem in der Tumorgenese und der Tumorprogression verschiedener Malignome eine besondere Bedeutung besitzt. Da die meisten Daten für gynäkologische Malignome vorliegen, konzentriert sich diese Übersicht auch auf die Bedeutung des Endothelinsystems bei Karzinomen des Eierstocks, des Gebärmutterhalses und der Brust. Die herausragende Rolle, die die Interaktion von ET-1 mit dem Endothelin-A-Rezeptor für die Karzinogenese und die Tumorprogression besitzt hat zu einer intensiven Suche nach entsprechenden Wirkstoffen geführt. Im Zuge dessen wurden selektive Endothelin-A-Rezeptor-Antagonisten sowie Inhibitoren des ECE-1 entwickelt. Die Hemmung des Endothelinsystems durch Blockade des Endothelin-A-Rezeptors oder von ECE-1 erscheint dabei als viel versprechender Ansatz für die zukünftige Therapie gynäkologischer Malignome. Die vorliegende Arbeit gibt einen umfassenden Überblick über die Bedeutung des Endothelinsystems in biologischen Systemen, beschreibt auf Grundlage
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