title: Menin immunoreactivity in secretory granules of human pancreatic islet cells.
abstract: The protein product of the Multiple Endocrine Neoplasia Type I (MEN1) gene is thought to be involved in predominantly nuclear functions; however, immunohistochemical (IHC) analysis data on cellular localization are conflicting. To further investigate menin expression, we analyzed human pancreas (an MEN1 target organ) using IHC analyses and 6 antibodies raised against full-length menin or its peptides. In 10 normal pancreas specimens, 2 independently raised antibodies showed unexpected cytoplasmic immunoreactivity in peripheral cells in each islet examined (over 100 total across all 10 patients). The staining exhibited a distinct punctate pattern and subsequent immunoelectron microscopy indicated the target antigen was in secretory granules. Exocrine pancreas and pancreatic stroma were not immunoreactive. In MEN1 patients, unaffected islets stained similar to those in normal samples but with a more peripheral location of positive cells, whereas hyperplastic islets and tumorlets showed increased and diffuse cytoplasmic staining, respectively. Endocrine tumors from MEN1 patients were negative for menin, consistent with a 2-hit loss of a tumor suppressor gene. Secretory granule localization of menin in a subset of islet cells suggests a function of the protein unique to a target organ of familial endocrine neoplasia, although the IHC data must be interpreted with some caution because of the possibility of antibody cross-reaction. The identity, cellular trafficking, and role of this putative secretory granule-form of menin warrant additional investigation.
authors.affiliation: *Department of Pathology, Wayne State University School of Medicine-Children's Hospital Michigan, Detroit, MI †Metabolic Diseases Branch, National Institute for Diabetes, Digestive and Kidney Disease ‡Pathogenetics Unit, Laboratory of Pathology ∥Laboratory of Pathology, National Cancer Institute §Histopathology Core, National Eye Institute, NIH, Bethesda, MD ¶Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Debelenko
authors.forename: Sunita
authors.initials: S
authors.lastname: Agarwal
authors.forename: Qiang
authors.initials: Q
authors.lastname: Du
authors.forename: Wusheng
authors.initials: W
authors.lastname: Yan
authors.forename: Heidi S
authors.initials: HS
authors.lastname: Erickson
authors.forename: Mones
authors.initials: M
authors.lastname: Abu-Asab
authors.forename: Mark A
authors.initials: MA
authors.lastname: Raffeld
authors.forename: Steven K
authors.initials: SK
authors.lastname: Libutti
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Marx
authors.forename: Michael R
authors.initials: MR
authors.lastname: Emmert-Buck
mesh_terms: D003429:Cross Reactions; D003593:Cytoplasm / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism*; D018761:Multiple Endocrine Neoplasia Type 1 / Q000473:pathology*; D010179:Pancreas / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism* / Q000473:pathology
chemical_list: C105373:MEN1 protein, human; D011518:Proto-Oncogene Proteins