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Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1.
Int J Cancer. 2007 Jan 15; 120(2):259-67.IJ

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.

Authors+Show Affiliations

Queensland Institute of Medical Research, Herston, QLD, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17044021

Citation

Loffler, Kelly A., et al. "Broad Tumor Spectrum in a Mouse Model of Multiple Endocrine Neoplasia Type 1." International Journal of Cancer, vol. 120, no. 2, 2007, pp. 259-67.
Loffler KA, Biondi CA, Gartside M, et al. Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1. Int J Cancer. 2007;120(2):259-67.
Loffler, K. A., Biondi, C. A., Gartside, M., Waring, P., Stark, M., Serewko-Auret, M. M., Muller, H. K., Hayward, N. K., & Kay, G. F. (2007). Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1. International Journal of Cancer, 120(2), 259-67.
Loffler KA, et al. Broad Tumor Spectrum in a Mouse Model of Multiple Endocrine Neoplasia Type 1. Int J Cancer. 2007 Jan 15;120(2):259-67. PubMed PMID: 17044021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1. AU - Loffler,Kelly A, AU - Biondi,Christine A, AU - Gartside,Michael, AU - Waring,Paul, AU - Stark,Mitchell, AU - Serewko-Auret,Magdalena M, AU - Muller,H Konrad, AU - Hayward,Nicholas K, AU - Kay,Graham F, PY - 2006/10/18/pubmed PY - 2007/2/24/medline PY - 2006/10/18/entrez SP - 259 EP - 67 JF - International journal of cancer JO - Int J Cancer VL - 120 IS - 2 N2 - 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. SN - 0020-7136 UR - https://www.unboundmedicine.com/medline/citation/17044021/Broad_tumor_spectrum_in_a_mouse_model_of_multiple_endocrine_neoplasia_type_1_ L2 - https://doi.org/10.1002/ijc.22288 DB - PRIME DP - Unbound Medicine ER -