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| Status |
Public on Dec 29, 2011 |
| Title |
p53 deletion induces liver carcinoma with bilineal differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Background and Aims: p53 can limit the self-renewal of stem cells from various tissues. Experimental evidence suggests that deletion of p53 can cooperate with other oncogenic events to induce aberrant self-renewal and transformation of progenitor cells. It is not known whether p53 deletion alone can lead to liver tumor formation.
Methods: We used AlfpCre mice for liver-specific deletion of Trp53 in a conditional knockout mouse model to analyze liver carcinogenesis.
Results: Here, we show that liver-specific deletion of p53 in mice consistently induces formation of liver carcinoma depicting bilineal differentiation. Freshly isolated p53-/- liver progenitor cells and hepatocytes exhibit chromosomal imbalances and an enhanced clonogenic capacity compared to p53-positive cells or p21-deficient cells. Primary cultures of hepatocytes and liver progenitor cells from p53-/- mice formed tumors with bilineal differentiation when transplanted into immuno-compromised mice. Together, these results indicate that loss of p53 alone is sufficient to induce primary liver cancer with bilineal differentiation originating from chromosomal instable cultured liver progenitor cells or hepatocytes.
Conclusions: The study shows that p53-dependent checkpoints inhibit transformation of liver progenitor cells and hepatocytes involving p21-independent mechanisms.
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| Overall design |
Liver tumors derived from Trp53 KO mice, liver tumors from DEN-treated wildtype mice, Trp53 KO liver and wildtype liver were isolated and RNA was extracted. Agilent-026655 Mouse 4x44K v2 arrays were used.
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| Contributor(s) |
Katz SF, Lechel A, Rudolph KL |
| Citation(s) |
22342966 |
| |
| Submission date |
Dec 28, 2011 |
| Last update date |
Nov 01, 2017 |
| 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 (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA150383 |
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