Multiple endocrine neoplasia type 1 (MEN1) is characterized by multiple tumors of the parathyroid, anterior pituitary and GI endocrine tissues. We have shown earlier that mutations in the MEN1 gene are responsible for the MEN1 syndrome, and the MEN1 encoded nuclear protein, Menin, binds the transcription factors JunD and NFkB, and can repress JunD and NFkB-induced transcription. We have developed both conventional and conditional mouse knockout models, which yield phenotypes that are remarkably similar to the human MEN1 disease, and has allowed us to delineate the stages in tumor development. In addition, we have developed tissue specific menin-inducible transgenic mouse models. Gene expression changes associated with the presence or absence of menin in mouse fibroblast cell lines and in islet cells at various stages of tumor formation are being studied. A model to re- express menin in knockout mice and to monitor the tumor growth/regression by a combination of histological analysis and non-invasive imaging methods is being developed. Efforts are underway to explore the role of menin on differentiation, if any, by inducing menin-null ES cells to differentiate into pancreatic islet cells. In addition, tissue specific transgenic expression and knockout models for MEN1 are also being developed in Drosophila. These models should help to understand the functional role(s) of menin.

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National Human Genome Research Institute (NHGRI)
Intramural Research (Z01)
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Human Genome Research
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Rodriguez, Virginia; Chen, Yidong; Elkahloun, Abdel et al. (2007) Chromosome 8 BAC array comparative genomic hybridization and expression analysis identify amplification and overexpression of TRMT12 in breast cancer. Genes Chromosomes Cancer 46:694-707
Ozawa, Atsushi; Agarwal, Sunita K; Mateo, Carmen M et al. (2007) The parathyroid/pituitary variant of multiple endocrine neoplasia type 1 usually has causes other than p27Kip1 mutations. J Clin Endocrinol Metab 92:1948-51
Ji, Youngmi; Prasad, Nijaguna B; Novotny, Elizabeth A et al. (2007) Mouse embryo fibroblasts lacking the tumor suppressor menin show altered expression of extracellular matrix protein genes. Mol Cancer Res 5:1041-51
Sun, Mei; Srikantan, Vasantha; Ma, Lanfeng et al. (2006) Characterization of frequently deleted 6q locus in prostate cancer. DNA Cell Biol 25:597-607
Sood, Raman; English, Milton A; Jones, MaryPat et al. (2006) Methods for reverse genetic screening in zebrafish by resequencing and TILLING. Methods 39:220-7
Scacheri, Peter C; Davis, Sean; Odom, Duncan T et al. (2006) Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis. PLoS Genet 2:e51
Cerrato, Aniello; Parisi, Michael; Santa Anna, Sonia et al. (2006) Genetic interactions between Drosophila melanogaster menin and Jun/Fos. Dev Biol 298:59-70
Agarwal, S K; Kennedy, P A; Scacheri, P C et al. (2005) Menin molecular interactions: insights into normal functions and tumorigenesis. Horm Metab Res 37:369-74
Zainabadi, Kayvan; Benyamini, Payam; Chakrabarti, Rita et al. (2005) A 700-kb physical and transcription map of the cervical cancer tumor suppressor gene locus on chromosome 11q13. Genomics 85:704-14
Agarwal, Sunita K; Lee Burns, A; Sukhodolets, Karen E et al. (2004) Molecular pathology of the MEN1 gene. Ann N Y Acad Sci 1014:189-98

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