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| Status |
Public on Aug 21, 2008 |
| Title |
SE2Fs Mediate A Fundamental Cell Cycle Deregulation in High-Grade Serous Ovarian Carcinomas |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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 oncologic feature.
Here, we attempted to clarify this issue by the examination of microarray expression profiles of SCAs (10 SCA1s, 15 SCA3s) and particularly by the comparison with another, less malignant, ovarian cancer type, serous borderline tumours (13 SBTs). Results were further validated by quantitative RT-PCR, both on the microarray samples and an independent panel. In addition, 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 a vast overexpression of E2F target genes in SCAs compared to SBTs. Overall, at least 45% of those genes with a significantly higher expression in SCAs were E2F targets. When taking into account the different SCA tumour grades, particularly SCA3s exhibited a major deregulated E2F target expression pattern, compared to SBTs. To a lesser extent, this was also the case for SCA1s, although the E2F target expression pattern of several SCA1s appeared to be more similar to SBTs. Generally, overexpression of E2F targets in SCAs appeared to be well-structured since those targets considered as 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 upregulated, 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
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| Overall design |
Expression levels of 13 SBTs, including 2 micropapillary SBTs (MPCs), 10 SCAs grade 1 (SCA1s), and 15 SCAs grade 3 (SCA3s) were compared.
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| Contributor(s) |
de Meyer T, Bijsmans I, van de Vijver KK, Bekaert S, Oosting J, van Criekinge W, van Engeland M, Sieben NL |
| Citation(s) |
18991331, 16087957 |
| Submission date |
Aug 18, 2008 |
| Last update date |
Jul 08, 2016 |
| Contact name |
Jan Oosting |
| Phone |
+31 71 5266619
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| Organization name |
Leiden University Medical Center
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| Department |
Pathology
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| Street address |
Albinusdreef 2
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| City |
Leiden |
| ZIP/Postal code |
2333ZA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL201 |
[HG-Focus] Affymetrix Human HG-Focus Target Array |
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| Samples (39)
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| Relations |
| BioProject |
PRJNA112941 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12471_RAW.tar |
51.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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