PMID- 17044021
OWN - NLM
STAT- MEDLINE
DCOM- 20070223
LR  - 20160303
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 120
IP  - 2
DP  - 2007 Jan 15
TI  - Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1.
PG  - 259-67
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an inherited cancer predisposition 
      syndrome typified by development of tumors in parathyroid, pituitary and 
      endocrine pancreas, as well as less common sites including both endocrine and 
      nonendocrine organs. Deletion or mutation of the tumor suppressor gene MEN1 on 
      chromosome 11 has been identified in many cases of MEN1 as well as in sporadic 
      tumors. The molecular biology of menin, the protein encoded by MEN1, remains 
      poorly understood. Here we describe a mouse model of MEN1 in which tumors were 
      seen in pancreatic islets, pituitary, thyroid and parathyroid, adrenal glands, 
      testes and ovaries. The observed tumor spectrum therefore includes types commonly 
      seen in MEN1 patients and additional types. Pancreatic pathology was most common, 
      evident in over 80% of animals, while other tumor types developed with lower 
      frequency and generally later onset. Tumors of multiple endocrine organs were 
      observed frequently, but progression to carcinoma and metastasis were not 
      evident. Tumors in all sites showed loss of heterozygosity at the Men1 locus, 
      though the frequency in testicular tumors was only 36%, indicating that a 
      different molecular mechanism of tumorigenesis occurs in those Leydig tumors that 
      do not show loss of the normal Men1 allele. Menin expression was below the level 
      of detection in ovary, thyroid and testis, but loss of nuclear menin 
      immunoreactivity was observed uniformly in all pancreatic islet adenomas and in 
      some hyperplastic islet cells, suggesting that complete loss of Men1 is a 
      critical point in islet tumor progression in this model.
CI  - (c) 2006 Wiley-Liss, Inc.
FAU - Loffler, Kelly A
AU  - Loffler KA
AD  - Queensland Institute of Medical Research, Herston, QLD, Australia.
FAU - Biondi, Christine A
AU  - Biondi CA
FAU - Gartside, Michael
AU  - Gartside M
FAU - Waring, Paul
AU  - Waring P
FAU - Stark, Mitchell
AU  - Stark M
FAU - Serewko-Auret, Magdalena M
AU  - Serewko-Auret MM
FAU - Muller, H Konrad
AU  - Muller HK
FAU - Hayward, Nicholas K
AU  - Hayward NK
FAU - Kay, Graham F
AU  - Kay GF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adenoma/chemistry/genetics/*pathology
MH  - Animals
MH  - DNA, Neoplasm/analysis
MH  - *Disease Models, Animal
MH  - Endocrine Gland Neoplasms/chemistry/genetics/*pathology
MH  - Exons/genetics
MH  - Female
MH  - Genes, Tumor Suppressor
MH  - Male
MH  - Mice/*genetics
MH  - Multiple Endocrine Neoplasia Type 1/chemistry/genetics/*pathology
MH  - Peptide Chain Initiation, Translational/genetics
MH  - Proto-Oncogene Proteins/analysis/*genetics
EDAT- 2006/10/18 09:00
MHDA- 2007/02/24 09:00
CRDT- 2006/10/18 09:00
PHST- 2006/10/18 09:00 [pubmed]
PHST- 2007/02/24 09:00 [medline]
PHST- 2006/10/18 09:00 [entrez]
AID - 10.1002/ijc.22288 [doi]
PST - ppublish
SO  - Int J Cancer. 2007 Jan 15;120(2):259-67. doi: 10.1002/ijc.22288.