title: Expression and functional analysis of menin in a multiple endocrine neoplasia type 1 (MEN1) patient with somatic loss of heterozygosity in chromosome 11q13 and unidentified germline mutation of the MEN1 gene.
abstract: In some patients with multiple endocrine neoplasia type 1 (MEN1) it is not possible to identify a germline mutation in the MEN1 gene. We sought to document the loss of expression and function of the MEN1 gene product, menin, in the tumors of such a patient. The proband is an elderly female patient with primary hyperparathyroidism, pancreatic islet tumor, and breast cancer. Her son has primary hyperparathyroidism. No germline MEN1 mutation was identified in the proband or her son. However, loss of heterozygosity at the MEN1 locus and complete lack of menin expression were demonstrated in the proband's tumor tissue. The proband's cultured parathyroid cells lacked the normal reduction in proliferation and parathyroid hormone secretion in response to transforming growth factor- beta. This assessment provided insight into the molecular pathogenesis of the patient and provides evidence for a critical requirement for menin in the antiproliferative action of transforming growth factor-beta.
authors.affiliation: Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Naito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaji
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sowa
authors.forename: Riko
authors.initials: R
authors.lastname: Kitazawa
authors.forename: Sohei
authors.initials: S
authors.lastname: Kitazawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Tsukada
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Hendy
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
mesh_terms: D000368:Aged; D002880:Chromosomes, Human, Pair 11; D005260:Female; D018095:Germ-Line Mutation / Q000502:physiology*; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology; D006980:Hyperthyroidism / Q000175:diagnosis / Q000235:genetics; D008113:Liver Neoplasms / Q000175:diagnosis; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D010281:Parathyroid Hormone / Q000378:metabolism; D010282:Parathyroid Neoplasms / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C105373:MEN1 protein, human; D010281:Parathyroid Hormone; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta