PMID- 16528608
OWN - NLM
STAT- MEDLINE
DCOM- 20060622
LR  - 20181113
IS  - 1389-9600 (Print)
IS  - 1389-9600 (Linking)
VI  - 5
IP  - 1
DP  - 2006
TI  - Analysis of p27(Kip1) expression in insulinomas developed in pancreatic beta-cell 
      specific Men1 mutant mice.
PG  - 49-54
AB  - Multiple Endocrine Neoplasia type 1 (MEN1) is a hereditary disease characterised 
      by the occurrence of multiple endocrine tumours. The biological functions of the 
      responsible gene, MEN1, and its encoded protein, menin, remain so far largely 
      elusive. The recent generation of Men1 mutant mice by our group and other 
      laboratories provides powerful tools allowing for the identification of cellular 
      and molecular events that occur after gene disruption. Interestingly, it has been 
      recently reported that p27(Kip1) expression is regulated by menin and that 
      decreased p27(Kip1) expression can be found in MEN1 insulinomas and parathyroid 
      adenomas. In order to address whether and when p27(Kip1) expression alters during 
      insulinoma development in pancreatic beta-cell-specific Men1 mutant mice, we 
      analysed p27(Kip1) expression in islet lesions from mutant mice at different 
      ages. Our data revealed that p27(Kip1) protein expression was reduced in 40 out 
      of 52 (77%) insulinomas analysed, whereas the remaining 12 insulinomas (23%) did 
      not show altered p27(Kip1) expression. No difference between the insulinomas with 
      and without decreased p27(Kip1) expression could be observed in terms of 
      histological features or menin inactivation. Furthermore, our analysis on 
      hyperplastic and dysplastic islets developed in young mutant mice showed the lack 
      of detectable alteration in p27(Kip1) expression, despite evident loss of menin 
      expression in a substantial proportion of islet cells. Our work confirms the 
      altered p27(Kip1) expression reported in tumours from MEN1 patients, whereas it 
      suggests that other molecular events may also participate in the tumorigenesis 
      process initiated by the Men1 gene inactivation.
FAU - Fontaniere, Sandra
AU  - Fontaniere S
AD  - Laboratoire Genetique Moleculaire, Signalisation et Cancer, CNRS, UMR5201, 
      Faculte de Medecine, Universite Claude Bernard Lyon 1, 69373, Lyon, France.
FAU - Casse, Huguette
AU  - Casse H
FAU - Bertolino, Philippe
AU  - Bertolino P
FAU - Zhang, Chang Xian
AU  - Zhang CX
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Fam Cancer
JT  - Familial cancer
JID - 100898211
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Survival
MH  - Cyclin-Dependent Kinase Inhibitor p27/*genetics
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Gene Deletion
MH  - *Gene Expression Regulation, Neoplastic
MH  - Immunohistochemistry
MH  - Insulinoma/*genetics/pathology
MH  - Islets of Langerhans/cytology
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/pathology
MH  - Pancreatic Neoplasms/*genetics/pathology
MH  - Probability
MH  - Proto-Oncogene Proteins/genetics
MH  - Sensitivity and Specificity
MH  - Tumor Cells, Cultured
EDAT- 2006/03/11 09:00
MHDA- 2006/06/23 09:00
CRDT- 2006/03/11 09:00
PHST- 2006/03/11 09:00 [pubmed]
PHST- 2006/06/23 09:00 [medline]
PHST- 2006/03/11 09:00 [entrez]
AID - 10.1007/s10689-005-2575-3 [doi]
PST - ppublish
SO  - Fam Cancer. 2006;5(1):49-54. doi: 10.1007/s10689-005-2575-3.