PMID- 12941803
OWN - NLM
STAT- MEDLINE
DCOM- 20030924
LR  - 20141120
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 16
DP  - 2003 Aug 15
TI  - Pancreatic beta-cell-specific ablation of the multiple endocrine neoplasia type 1 
      (MEN1) gene causes full penetrance of insulinoma development in mice.
PG  - 4836-41
AB  - The function of the predisposition gene to multiple endocrine neoplasia type 1 
      (MEN1) syndrome remains largely unknown. Previous studies demonstrated that null 
      mutation of the Men1 gene caused mid-gestation lethality in mice, whereas 
      heterozygous Men1 knockout mice developed multiple endocrine tumors late in life. 
      To seek direct evidence on the causal role of menin in suppressing tumor 
      development, we generated mice in which the Men1 gene was disrupted specifically 
      in pancreatic beta cells. These mice began to develop hyperplastic islets at as 
      early as 2 months of age and insulinomas at 6 months of age. The islet lesions 
      exhibited features of multistage tumor progression, including beta-cell 
      dedifferentiation, angiogenesis, and altered expression of both E-cadherin and 
      beta-catenin. Additionally, disturbance of blood insulin and glucose levels 
      correlated with tumor development, mimicking human MEN1 symptoms. Our data 
      indicate that this strain of mice provides a powerful tool for the study of the 
      mechanisms of tumorigenesis related to MEN1 disease.
FAU - Bertolino, Philippe
AU  - Bertolino P
AD  - Genetic and Cancer Laboratory, CNRS, UMR5641, Faculty of Medicine University Lyon 
      1, 69373, Lyon, France.
FAU - Tong, Wei-Min
AU  - Tong WM
FAU - Herrera, Pedro Luis
AU  - Herrera PL
FAU - Casse, Huguette
AU  - Casse H
FAU - Zhang, Chang Xian
AU  - Zhang CX
FAU - Wang, Zhao-Qi
AU  - Wang ZQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Blood Glucose)
RN  - 0 (CTNNB1 protein, mouse)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Insulin)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Animals
MH  - Blood Glucose/analysis
MH  - Cytoskeletal Proteins/analysis
MH  - Gene Deletion
MH  - Insulin/blood
MH  - Insulinoma/*etiology
MH  - Islets of Langerhans/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neoplasm Proteins/*genetics
MH  - Pancreatic Neoplasms/*etiology
MH  - *Proto-Oncogene Proteins
MH  - Trans-Activators/analysis
MH  - beta Catenin
EDAT- 2003/08/28 05:00
MHDA- 2003/09/25 05:00
CRDT- 2003/08/28 05:00
PHST- 2003/08/28 05:00 [pubmed]
PHST- 2003/09/25 05:00 [medline]
PHST- 2003/08/28 05:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Aug 15;63(16):4836-41.