Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10905756 | Experimental Cell Research | 2005 | 10 Pages |
Abstract
Constitutive activation of the ras oncoprotein plays a critical role in cancer invasion and metastasis. Particularly, ras-related protease expression such as the serine protease urokinase plasminogen activator (u-PA) has been implicated in mediating cancer cell invasion. Previous studies have shown that ras-mediated u-PA expression is regulated through the mitogen- (MAPK) and stress-activated protein kinase (SAPK) signal transduction pathways extracellular signal-regulated kinase (ERK) and c-Jun-activating kinase (JNK). We therefore asked the question, if ras-related cell invasion might additionally require the third MAPK/SAPK signal transduction cascade, p38. Indeed, we found that ras induces invasion based on the activation of certain p38 protein kinase isoforms, in particular, p38α. Moreover, ras activation through transient or stable expression of a Ha-rasEJ mutant induced the expression of u-PA. This was found to be a consequence of an increase of u-PA m-RNA, which was paralleled by only a modest activation of the u-PA promoter. In conclusion, we provide evidence for the requirement of a novel ras-p38α-u-PA pathway for ras-dependent cellular invasion.
Keywords
GFPRASSfMERKp38AP-1CATSOSNIH3T3FBSJnkSAPK3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromideDMSOMAPKMKKMTTu-PAInvasionDimethylsulfoxideLSMfetal bovine serumactivating protein 1urokinase plasminogen activatorSerum-free mediumgreen fluorescent proteinmitogen-activated protein kinaseStress-activated protein kinasemitogen-activated protein kinase kinaseson of sevenlesschloramphenicol acetyl transferaseextracellular signal-regulated kinase
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Cancer Research
Authors
Andreas Behren, Konrad Binder, Goran Vucelic, Stephan Herberhold, Bernhard Hirt, Hubert Loewenheim, Serena Preyer, Hans Peter Zenner, Christian Simon,