The MEN1 gene is a likely tumor suppressor gene because tumors in multiple endocrine neoplasia type 1 (MEN1) show loss of heterozygosity (LOH) at this locus and because sporadic tumors of the same tissues also show 11q13 LOH implicating this gene through a similar mechanism. We have contributed to an intramural NIH collaboration that has cloned the MEN1 gene. We are continuing to explore its clinical and its basic implications. We have proven that it causes nonendocrine tumors (angiofibroma, collagenoma, and leiomyoma). We find germline mutations in 90-95% of probands with familial MEN1 or with sporadic MEN1. In contrast, probands with familial isolated hyperparathyroidism have not shown MEN1 mutations. We will continue to explore these and other states for germline MEN1 mutations. We have also found somatic MEN1 mutation in 15 to 35% of sporadic tumors of many endocrine organs. We will also determine the spectrum of pathologic states that MEN1 gene contributes to through mutation and other mechanisms. We have also initiated studies on the expression and actions of the encoded menin RNA and protein. The gene has been expressed in E. Coli and mammalian cells and will be overexpressed in insect cells. And vector constructs are being developed to express mutant forms. The MEN1-encoded protein is called """"""""menin"""""""". We have identified menin interaction with the nuclear transcription factors junD, NF-kappaB, and other interactions are being sought. These studies should help identify its biochemical activities. Heterozygous knockout in the mouse is a useful model under evaluation.
| 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 |
| Marx, Stephen J; Simonds, William F (2006) Editorial: Imaging to detect early endocrine cancers. J Clin Endocrinol Metab 91:2861-3 |
| 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 |
| Marx, Stephen J (2005) Molecular genetics of multiple endocrine neoplasia types 1 and 2. Nat Rev Cancer 5:367-75 |
| Marx, S J; Stratakis, C A (2005) Multiple endocrine neoplasia--introduction. J Intern Med 257:2-5 |
| Marx, Stephen J; Simonds, William F (2005) Hereditary hormone excess: genes, molecular pathways, and syndromes. Endocr Rev 26:615-61 |
| 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 |
| 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 |
| Scacheri, Peter C; Crabtree, Judy S; Kennedy, Alyssa L et al. (2004) Homozygous loss of menin is well tolerated in liver, a tissue not affected in MEN1. Mamm Genome 15:872-7 |
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