Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1

Loffler, Kelly A., Biondi, Christine A., Gartside, Michael, Waring, Paul, Stark, Mitchell, Serewko-Auret, Magdalena M., Muller, H. Konrad, Hayward, Nicholas K. and Kay, Graham F. (2007) Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1. International Journal of Cancer, 120 2: 259-267. doi:10.1002/ijc.22288

Author Loffler, Kelly A.
Biondi, Christine A.
Gartside, Michael
Waring, Paul
Stark, Mitchell
Serewko-Auret, Magdalena M.
Muller, H. Konrad
Hayward, Nicholas K.
Kay, Graham F.
Title Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 1097-0215
Publication date 2007-01-15
Year available 2006
Sub-type Article (original research)
DOI 10.1002/ijc.22288
Open Access Status DOI
Volume 120
Issue 2
Start page 259
End page 267
Total pages 9
Place of publication Hoboken, NJ, United States
Publisher John Wiley and Sons
Language eng
Subject 111201 Cancer Cell Biology
111203 Cancer Genetics
Formatted abstract
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.
Keyword Endocrine
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Issue section: "Cancer Cell Biology"

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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Created: Tue, 24 Mar 2009, 21:36:58 EST by Ms Lynette Adams on behalf of Medicine - Royal Brisbane and Women's Hospital