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Die K-ras induzierte, serratierte Kolonkarzinogenese: Untersuchung zur Funktion von onkogenem K-ras in der intestinalen Karzinogenese mit besonderem Bezug auf Seneszenz und Proliferation

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Description

KRAS-Mutationen treten in nahezu 50% aller Kolontumore auf. In einem Mausmodell der Kolonkarzinogenese führt die Expression von onkogenem K-rasG12D in Enterozyten zur Bildung einer serratierten Hyperplasie im Kolonepithel. Ein Tumorwachstum ist jedoch aufgrund einer Erk1/2-vermittelten Induktion von Onkogen-induzierter Seneszenz und einer gesteigerten Expression des Zellzyklusinhibitors p16Ink4a in diesen Zellen gehemmt. Eine Kombination der Expression des K-rasG12D-Onkogens mit einer Deletion des p16Ink4a/Arf-Lokus in der Maus führt zur Aufhebung des Wachstumsarrests und ermöglicht die Bildung von invasiven Karzinomen im proximalen Kolon. Diese Tumore gleichen sowohl histologisch als auch molekular den humanen serratierten Adenomen und stellen eine distinkte Tumorentität dar. Die Karzinome entwickeln sich – anders als klassiche, APC-mutierte Kolonkarzinome - unabhängig von der Aktivierung des Wnt-Signalweges. Die Arbeit stellt die K-rasG12D-Maus als ein erstes Modell zur Untersuchung von serratierten Adenomen vor und zeigt die Ras-Raf-Mek-Erk-Signalkaskade als Initiator einer alternativen kolorektalen Karzinogenese.

Product Specifications

Format
paperback
Domain
Amazon UK
Release Date
12 July 2010
Listed Since
16 July 2010

Barcode

No barcode data available

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