PMID- 22342966
OWN - NLM
STAT- MEDLINE
DCOM- 20120618
LR  - 20240104
IS  - 1528-0012 (Electronic)
IS  - 0016-5085 (Linking)
VI  - 142
IP  - 5
DP  - 2012 May
TI  - Disruption of Trp53 in livers of mice induces formation of carcinomas with 
      bilineal differentiation.
PG  - 1229-1239.e3
LID - 10.1053/j.gastro.2012.02.009 [doi]
AB  - BACKGROUND & AIMS: p53 limits the self-renewal of stem cells from various 
      tissues. Loss of p53, in combination with other oncogenic events, results in 
      aberrant self-renewal and transformation of progenitor cells. It is not known 
      whether loss of p53 is sufficient to induce tumor formation in liver. METHODS: We 
      used AlfpCre mice to create mice with liver-specific disruption of Trp53 
      (AlfpCre(+)Trp53(Delta2-10/Delta2-10) mice). We analyzed colony formation and genomic 
      features and gene expression patterns in liver cells during hepatocarcinogenesis 
      in mice with homozygous, heterozygous, and no disruption of Trp53. RESULTS: 
      Liver-specific disruption of Trp53 consistently induced formation of liver 
      carcinomas that had bilineal differentiation. In nontransformed liver cells and 
      cultured primary liver cells, loss of p53 (but not p21) resulted in chromosomal 
      imbalances and increased clonogenic capacity of liver progenitor cells (LPCs) and 
      hepatocytes. Primary cultures of hepatocytes and LPCs from 
      AlfpCre(+)Trp53(Delta2-10/Delta2-10) mice, but not Cdkn1a(-/-) mice, formed tumors with 
      bilineal differentiation when transplanted into immunocompromised mice. 
      Spontaneous liver tumors that developed in AlfpCre(+)Trp53(Delta2-10/Delta2-10) mice had 
      significant but complex alterations in expression of Rb checkpoint genes compared 
      with chemically induced liver tumors that developed mice with wild-type Trp53. 
      CONCLUSIONS: Deletion of p53 from livers of mice is sufficient to induce tumor 
      formation. The tumors have bilineal differentiation and dysregulation of Rb 
      checkpoint genes.
CI  - Copyright (c) 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.
FAU - Katz, Sarah-Fee
AU  - Katz SF
AD  - Institute of Molecular Medicine and Max Planck Research Group on Stem Cell Aging, 
      University of Ulm, Ulm, Germany.
FAU - Lechel, Andre
AU  - Lechel A
FAU - Obenauf, Anna C
AU  - Obenauf AC
FAU - Begus-Nahrmann, Yvonne
AU  - Begus-Nahrmann Y
FAU - Kraus, Johann M
AU  - Kraus JM
FAU - Hoffmann, Eva M
AU  - Hoffmann EM
FAU - Duda, Johanna
AU  - Duda J
FAU - Eshraghi, Parisa
AU  - Eshraghi P
FAU - Hartmann, Daniel
AU  - Hartmann D
FAU - Liss, Birgit
AU  - Liss B
FAU - Schirmacher, Peter
AU  - Schirmacher P
FAU - Kestler, Hans A
AU  - Kestler HA
FAU - Speicher, Michael R
AU  - Speicher MR
FAU - Rudolph, K Lenhard
AU  - Rudolph KL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120215
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (CDKN1A protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
CIN - Gastroenterology. 2012 May;142(5):1066-9. PMID: 22449579
MH  - Aging
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Transformation, Neoplastic
MH  - Chromosomal Instability
MH  - Cyclin-Dependent Kinase Inhibitor p21/physiology
MH  - Genes, Retinoblastoma
MH  - Liver/*pathology
MH  - Liver Neoplasms, Experimental/*etiology/genetics/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Tumor Suppressor Protein p53/*physiology
EDAT- 2012/02/22 06:00
MHDA- 2012/06/19 06:00
CRDT- 2012/02/21 06:00
PHST- 2011/06/16 00:00 [received]
PHST- 2012/01/20 00:00 [revised]
PHST- 2012/02/07 00:00 [accepted]
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/06/19 06:00 [medline]
AID - S0016-5085(12)00204-1 [pii]
AID - 10.1053/j.gastro.2012.02.009 [doi]
PST - ppublish
SO  - Gastroenterology. 2012 May;142(5):1229-1239.e3. doi: 
      10.1053/j.gastro.2012.02.009. Epub 2012 Feb 15.