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| Status |
Public on Mar 31, 2012 |
| Title |
Transient telomere dysfunction induces chromosomal instability and promotes carcinogenesis in telomerase-proficient mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
Genome variation profiling by array
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| Summary |
Background and Aims: Telomere dysfunction can increase tumor initiation by induction of chromosomal instability, but initiated tumor cells need to reactivate telomerase for genome stabilization and tumor progression. However, this concept has not been proven in vivo since appropriate mouse models were lacking. Here, we analyzed hepatocarcinogenesis (i) in a novel mouse model of inducible telomere dysfunction on a telomerase-proficient background, (ii) in telomerase knockout mice with chronic telomere dysfunction (G3 mTerc-/-), and (iii) in wild-type mice with functional telomeres and telomerase. Transient or chronic telomere dysfunction enhanced the rates of chromosomal aberrations during hepatocarcinogenesis, but only telomerase-proficient mice exhibited significantly increased rates of macroscopic tumor formation and cancer cell proliferation in response to telomere dysfunction. In contrast, telomere dysfunction resulted in pronounced accumulation of DNA damage, cell cycle arrest and apoptosis in telomerase-deficient liver tumors. Together, these data provide the first in vivo evidence that transient telomere dysfunction during early and late stages of tumorigenesis can promote chromosomal instability and carcinogenesis in telomerase-proficient mice in the absence of additional genetic checkpoint defects at germline level.
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| Overall design |
RNA from liver tumors derived from from DEN treated TTD+ mice TTD- mice and RNA from normal liver 48h-72h after doxycycline induced transient telomere dysfunction in TTD+ and TTD- liver were isolated and RNA was extracted. Agilent Mouse 4x44K v2 arrays were used. DNA from liver tumors and corrresponding kidney as control derived from from DEN treated TTD+ mice, TTD- mice and mTERC-/- G3 mice was isolated and extracted using Phenol/Chloroform. Agilent Mouse 4x44K and Mouse 1x244K arrays were used.
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| Contributor(s) |
Begus-Nahrmann Y, Lechel A, Rudolph KL |
| Citation(s) |
22622037 |
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| Submission date |
Mar 26, 2012 |
| Last update date |
Aug 27, 2019 |
| Contact name |
Hans A Kestler |
| E-mail(s) |
[email protected]
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| Phone |
+49 731 5024248
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| Organization name |
University of Ulm
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| Department |
Research Group Bioinformatics and Systems Biology
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| Street address |
Albert-Einstein-Allee 11
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| City |
Ulm |
| ZIP/Postal code |
89081 |
| Country |
Germany |
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| Platforms (3) |
| GPL4092 |
Agilent-014695 Mouse Genome CGH Microarray 244A (G4415A) (Feature Number version) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
| GPL11288 |
Agilent-015028 Mouse Genome CGH Microarray 4x44K (Feature Number version) |
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| Samples (38)
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| Relations |
| BioProject |
PRJNA157343 |
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