title: Cyclin E dysregulation and chromosomal instability in endometrial cancer.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Innsbruck University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hubalek
authors.forename: Andreas
authors.initials: A
authors.lastname: Widschwendter
authors.forename: Martin
authors.initials: M
authors.lastname: Erdel
authors.forename: Andreas
authors.initials: A
authors.lastname: Gschwendtner
authors.forename: Heidi M
authors.initials: HM
authors.lastname: Fiegl
authors.forename: Hannes M
authors.initials: HM
authors.lastname: Müller
authors.forename: Georg
authors.initials: G
authors.lastname: Goebel
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mueller-Holzner
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.forename: Charles H
authors.initials: CH
authors.lastname: Spruck
authors.forename: Steven I
authors.initials: SI
authors.lastname: Reed
authors.forename: Martin
authors.initials: M
authors.lastname: Widschwendter
mesh_terms: D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D043171:Chromosomal Instability / Q000235:genetics / Q000502:physiology*; D019927:Cyclin E / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence
chemical_list: D019927:Cyclin E