Cyclin E dysregulation and chromosomal instability in endometrial cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-05

AUTHORS

Michael M Hubalek, Andreas Widschwendter, Martin Erdel, Andreas Gschwendtner, Heidi M Fiegl, Hannes M Müller, Georg Goebel, Elisabeth Mueller-Holzner, Christian Marth, Charles H Spruck, Steven I Reed, Martin Widschwendter

ABSTRACT

Deregulation of cyclin E, an activator of cyclin-dependent kinase 2 (Cdk2), has been associated with a broad spectrum of human malignancies. Yet the mechanism linking abnormal cyclin E expression to carcinogenesis is largely unknown. The gene encoding the F-box protein hCdc4, a key component of the molecular machinery that targets cyclin E for degradation, is frequently mutated in endometrial cancer, leading to deregulation of cyclin E expression. Here we show that hCDC4 gene mutation and hyperphosphorylation of cyclin E, a parameter that usually correlates with hCDC4 mutation, have a strong statistically significant association with polypoidy and aneuploidy in endometrial cancer. On the contrary, elevated expression of cyclin E by itself was not significantly correlated with polyploidy or aneuploidy when tumors of similar grade are evaluated. These data suggest that impairment of cell cycle regulated proteolysis of cyclin E may be linked to carcinogenesis by promoting genomic instability. More... »

PAGES

1207560

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1207560

DOI

http://dx.doi.org/10.1038/sj.onc.1207560

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000208682

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15048079


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