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Multiple Endocrine Neoplasia Type 1

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Principles of Molecular Medicine

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is characterized by the combined occurrence of tumors of the parathyroids, pancreatic islets, and anterior pituitary. In addition, some patients may also develop adrenal cortical, carcinoid, facial angiofibromas, collageno-mas, and lipomatons tumors. MEN1 is inherited as an autosomal-dominant disorder and the gene causing MEN1 is located on chromosome 11q13. The MEN1 gene consists of 10 exons that encode a 610 amino acid protein, menin, which has a role in transcriptional regulation and genome stability. The mutations causing MEN1 are of diverse types and are scattered throughout the coding region. Mice deleted for a MEN1 allele develop endocrine tumors similar to those found in MEN1 patients. The availability of these mouse models for MEN1 will help to further elucidate the role of menin in regulating cell proliferation.

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Selected References

  • Agarwal SK, Guru SC, Heppner C, et al. Menin interacts with the AP1 transcription factor JunD and represses JunD-activated transcription. Cell 1999;84:730–735.

    Google Scholar 

  • Agarwal SK, Kester MB, Deblenko LV, et al. Germline mutations of the MEN1 gene in familial multiple endocrine neoplasia type 1 and related states. Hum Mol Genet 1997;6:1169-1175.

    Google Scholar 

  • Bassett JH, Rashbass P, Harding B, Forbes SA, Pannett AA, Thakker RV. Studies of the murine homolog of the multiple endocrine neoplasia type 1 (MEN1) gene, MEN1. J Bone Miner Res 1999;14:3–10.

    Article  CAS  Google Scholar 

  • Bassett JHD, Forbes SA, Pannett AAJ, et al. Characterisation of mutations in patients with multiple endocrine neoplasia type 1 (MEN1). Am J Hum Genet 1998;62:232–244.

    Article  PubMed  CAS  Google Scholar 

  • Bertolino P, Radovanovic I, Casse H, Aguzzi A, Wang Z-Q, Zhang C-X. Genetic ablation of the tumor suppressor menin causes lethality at mid-gestation with defects in multiple organs. Mech Dev 2003;120: 549–560.

    Article  PubMed  CAS  Google Scholar 

  • Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001;86(12): 5658–5671.

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekharappa SC, Guru SC, Manickam P, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 1997;276: 404–407.

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekharappa SC, Teh BT. Functional studies of the MEN1 gene. J Med 2003;253:606–615.

    CAS  Google Scholar 

  • Crabtree JS, Scacheri PC, Ward JM, et al. A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. Proc Natl Acad Sci USA 2001;98:1118–1123.

    Article  PubMed  CAS  Google Scholar 

  • Darling TN, Skarulis MC, Steinberg SM, Marx SJ, Spiegel AM, Turner M. Multiple facial angiofibromas and collagenomas in patients with multi-ple endocrine neoplasia type 1. Arch Dermatol 1997;133:853–861.

    Article  PubMed  CAS  Google Scholar 

  • Guru SC, Goldsmith PK, Burns AL, et al. Menin, the product of the MEN1 gene, is a nuclear protein. Proc Natl Acad Sci USA 1998;b:1630–1634.

    Google Scholar 

  • Heppner C, Bilimoria KY, Agarwal SK, et al. The tumour suppressor protein and inhibits NF-kappaB-mediated transactivation. Oncogene 2001;20(36):4917–4925.

    Article  PubMed  CAS  Google Scholar 

  • Jensen RT. Management of the Zollinger-Ellison syndrome in patients with multiple endocrine neoplasia type 1. J Intern Med 1998;243:477–488.

    Article  PubMed  CAS  Google Scholar 

  • Kaji H, Canaff L, Lebrun JJ, Goltzman D, Hendy GN. Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signalling. Proc Natl Acad Sci USA 2001;98(7):3837–2842.

    Article  PubMed  CAS  Google Scholar 

  • Knudson AG. Antioncogenes and human cancer. Proc Natl Acad Sci USA 1993;90:10914–10921.

    Article  PubMed  CAS  Google Scholar 

  • Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjold MC. Multiple endocrine neoplasia type I gene maps to chromosome 11 and is lost in insulinoma. Nature 1988;332:85–87.

    Article  PubMed  CAS  Google Scholar 

  • Lemmens IH, Forsberg L, Pannett AA, et al. Menin interacts directly with the homeobox-containing protein Pem. Biochem Biophys Res Commun 2001;286:426–431.

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Egido J, Cunningham J, Berg M, Oberg K, Bongcam-Rudloff E, Gobl A. Menin’s interaction with glial fibrillary acidic protein and vimentin suggests a role for the intermediate filament network in regulating menin activity. Exp Cell Res 2002;278:175–183.

    Article  PubMed  CAS  Google Scholar 

  • Marx SJ. Multiple Endocrine Neoplasia Type 1. In: Vogelstein B, Kinzler KW, eds. Genetic Basis of Human Cancer, New York: McGraw Hill, 1998; pp. 489–506.

    Google Scholar 

  • Norton JA, Fraker DL, Alexander R, et al. Surgery to cure the Zollinger-Ellison syndrome. N Engl J Med 1999;341:635–644.

    Article  PubMed  CAS  Google Scholar 

  • Ohkura N, Kishi M, Tsukada T, Yamaguchi K. Menin. A gene product responsible for multiple endocrine neoplasia type 1, interacts with the putative tumor metastasis suppressor nm23. Biochem Biophys Res Commun 2001;282:1206–1210.

    Article  PubMed  CAS  Google Scholar 

  • Olufenic SE, Green JS, Manikam P, et al. Common ancestral mutation in the MEN1 gene is likely responsible for the prolactinoma variant of MEN1 (MEN1 burin) in four kindreds from Newfoundland. Hum Mutat 1998; 11:204–269.

    Google Scholar 

  • Pannett AAJ, Kennedy AM, Turner JJO, et al. Multiple endocrine neoplasia type 1 (MEN1) germline mutations in familial isolated primary hyperparathyroidism. Clin Endocrinol (Oxf) 2003;58:639–646.

    Article  CAS  Google Scholar 

  • Pannett AAJ, Thakker RVT. Multiple endocrine neoplasia type 1 (MEN1) gene. Endocr Relat Cancer 1999;6:449–473.

    Article  PubMed  CAS  Google Scholar 

  • Scacheri PC, Crabtree JS, Novotny EA, et al. Bidirectional transcriptional activity of PGK-neomycin and unexpected embryonic lethality in heterozygote chimeric knockout mice. Genesis 2001;30:259–263.

    Article  PubMed  CAS  Google Scholar 

  • Skogseid B, Larsson C, Lindgren PG, et al. Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 1992;75:76–81.

    Article  PubMed  CAS  Google Scholar 

  • Skogseid B, Oberg K, Benson L, et al. A standardized meal stimulation test of the endocrine pancreas for early detection of pancreatic endocrine tumors in multiple endocrine neoplasia type 1 syndrome: five years experience. J Clin Endocrinol Metab 1987;64:1233–1240.

    Article  PubMed  CAS  Google Scholar 

  • Sowa H, Kaji H, Canaff L, et al. Inactivation of menin, the product of multiple endocrine neoplasia type 1 gene, inhibits the commitment of mul-tipotential mesenchymal stem cells into the osteoblast lineage. J Biol Chem 2003;23:21,058–21,069.

    Article  CAS  Google Scholar 

  • Stewart C, Parente F, Piehl F, et al. Characterisation of the mouse MEN1 gene and its expression during development. Oncogene 1998;17: 2485–2493.

    Article  PubMed  CAS  Google Scholar 

  • Sukhodolets KE, Hickman AB, Agarwal SK, et al. The 32-kilodalton sub-unit of replication protein A interacts with menin, the product of the MEN1 tumour suppressor gene. Mol Cell Biol 2003;23:493–509.

    Article  PubMed  CAS  Google Scholar 

  • Teh BT, Kytola S, Farnebo F, et al. Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism. J Clin Endocrinol Metab 1998;83: 2621–2626.

    Article  PubMed  CAS  Google Scholar 

  • Teh BT, Zedenius J, Kytola S, et al. Thymic carcinoids in multiple endocrine neoplasia type 1. Ann Surg 1998;228:99–105.

    Article  PubMed  CAS  Google Scholar 

  • Thakker RV. The molecular genetics of the multiple endocrine neoplasia syndromes. Clin Endocrinol (Oxf) 1993;39:1–14.

    Google Scholar 

  • Thakker RV. Multiple Endocrine Neoplasia Type 1 (MEN1). In: DeGroot LJ, Besser GK, Burger HG, et al. eds. Endocrinology, Philadelphia: WB Saunders, 2000; 2815–2831.

    Google Scholar 

  • The European Consortium on MEN1. Identification of the multiple endocrine neoplasia Type 1 (MEN1) gene. Hum Mol Genet 1997;6: 1177–1183.

    Article  Google Scholar 

  • Tomassetti P, Migliori M, Caletti GC, Fusaroli P, Corinaldesi R, Gullo L. Treatment of type II gastric carcinoid tumors with somatostatin analogues. N Engl J Med 2000;343:551–554.

    Article  PubMed  CAS  Google Scholar 

  • Trump D, Farren B, Wooding C, et al. Clinical studies of multiple endocrine neoplasia type 1 (MEN1) in 220 patients. Q J Med 1996;89: 653–669.

    CAS  Google Scholar 

  • Wolfe MM, Jensen RT. Zollinger-Ellison syndrome. Current concepts in diagnosis and management. N Engl J Med 1987;317:1200–1209.

    Article  PubMed  CAS  Google Scholar 

  • Yaguchi H, Ohkura N, Tsukada K. Menin, the multiple endocrine neoplasia type 1 gene product, exhibits GTP-hydrolyzing activity in the presence of the tumor metastasis suppressor nm23. J Biol Chem 2002; 277:38,197–38,204.

    Article  PubMed  CAS  Google Scholar 

  • Yamita W, Ikeo Y, Yamauchik K, Sakurai A, Hashizumek K. Suppression of insulin-induced AP-1 transactivation by menin accompanies inhibition of c-Fos induction. Int J Cancer 2003;103:738–744.

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Nuffield Department of Clinical Medicine, University of Oxford, Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford, UK

    Rajesh V. Thakker Md, FRCP

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  1. Rajesh V. Thakker Md, FRCP
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Editors and Affiliations

  1. Department of Medicine, Division of Cardiology Carolina Cardiovascular Biology Center, University of North Carolina School of Medicine, Chapel Hill, NC

    Marschall S. Runge MD, PhD  & Cam Patterson MD  & 

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© 2006 Humana Press Inc.

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Thakker, R.V. (2006). Multiple Endocrine Neoplasia Type 1. In: Runge, M.S., Patterson, C. (eds) Principles of Molecular Medicine. Humana Press. https://doi.org/10.1007/978-1-59259-963-9_39

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  • DOI: https://doi.org/10.1007/978-1-59259-963-9_39

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-202-5

  • Online ISBN: 978-1-59259-963-9

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