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| Status |
Public on May 23, 2016 |
| Title |
Gene dosage imbalance contributes to chromosomal instability-induced tumorigenesis |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by array
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| Summary |
Chromosomal instability (CIN) is thought to be a source of mutability in human cancer. However, CIN is highly deleterious for the cell, and the resulting aneuploidy induces metabolic stress and compromises cell fitness. Here we utilized the X-chromosome dosage compensation mechanism and changes in X-chromosome number to demonstrate in Drosophila epithelial cells the causal relationship between CIN, aneuploidy, gene dosage imbalance and tumorigenesis. Whereas the harmful effects of CIN can be buffered by resetting the X-chromosome dosage compensation to compensate for changes in X-chromosome number, interfering with the mechanisms of dosage compensation suffices to induce tumorigenesis. In addition, multiple mechanisms buffer the deleterious effects of CIN including DNA-damage repair, activation of the p38 signalling pathway, and induction of cytokine expression to promote compensatory cell proliferation. These data reveal a key role of gene dosage imbalances to CIN-induced programmed cell death and tumorigenesis and the existence of robust compensatory mechanisms.
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| Overall design |
Wing imaginal discs expressing p35, a dsRNA form of asp (ID 110177, VDRC) and UAS-RFP (ID 31417, Bloomington Stock Center) under the control of the en-gal4 driver and carrying an MMP1-GFP reporter construct (Wang et al., 2010) were dissected from ~8-day-old larvae. Cells from the anterior compartment (RFP-negative, MMP1-GFP-negative), posterior compartment (RFP-positive, MMP1-GFP-negative) and delaminating cell population (RFP-positive, MMP1-GFP-positive) were sorted by FACS. Differential expression was performed between the cell populations. 3 biological replicates per cell population.
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| Contributor(s) |
Stephan-Otto Attolini C, Rodolosse A, Clemente-Ruiz M, Milan M |
| Citation(s) |
26859353 |
| Submission date |
Jul 22, 2015 |
| Last update date |
May 04, 2018 |
| Contact name |
Camille Stephan Otto Attolini |
| Organization name |
IRB Barcelona
|
| Department |
Biostatistics and bioinformatics Unit
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| Street address |
Baldiri Reixac 10
|
| City |
Barcelona |
| State/province |
Select a State or Province |
| ZIP/Postal code |
08028 |
| Country |
Spain |
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| Platforms (1) |
| GPL1322 |
[Drosophila_2] Affymetrix Drosophila Genome 2.0 Array |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA290657 |
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