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E2F s mediate a fundamental cell‐cycle deregulation in high‐grade serous ovarian carcinomas
Author(s) -
De Meyer T,
Bijsmans ITGW,
Van de Vijver KK,
Bekaert S,
Oosting J,
Van Criekinge W,
van Engeland M,
Sieben NLG
Publication year - 2009
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2452
Subject(s) - e2f , cancer research , ovarian cancer , serous fluid , biology , cell cycle , transcription factor , tissue microarray , cancer , gene , genetics , biochemistry
Several studies described a role for the E2F/Rb pathway in ovarian serous carcinomas (SCAs). Since E2F/Rb pathway deregulation is a general hallmark of human cancer, it remains unclear whether this deregulation is of particular importance in SCAs or whether it reflects a common oncological feature. Here, we have clarified this issue by the examination of microarray expression profiles of SCAs and particularly by the comparison with another, less malignant, ovarian cancer type, serous borderline tumours (SBTs). Results were validated by quantitative RT‐PCR, both on the microarray samples and on an independent panel, and TP53 mutation analysis was performed. This integrated analysis revealed a significant increase in the expression of the transcription factors E2F1 and E2F3 in SCAs, when compared to SBTs. This was associated with vast overexpression of E2F target genes in SCAs compared to SBTs. High‐grade SCAs in particular exhibited a major deregulated E2F target expression pattern. Generally, overexpression of E2F targets in SCAs appeared to be well structured since those targets considered negative regulators of the cell cycle or promoters of apoptosis were usually not overexpressed in SCAs. Similar to E2F target deregulation, TP53 mutations were identified in SCA3s, to a lesser extent in SCA1s, and not in SBTs. These results suggest that a structured, generally up‐regulated E2F transcription factor activity is associated with a global cell‐cycle disturbance in high‐grade SCAs and exceeds typical E2F/Rb pathway disruption in tumours, at least compared with SBTs. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.