title: Conditional deletion of Men1 in the pancreatic β-cell leads to glucagon-expressing tumor development.
abstract: The tumor suppressor menin is recognized as a key regulator of β-cell proliferation. To induce tumorigenesis within the pancreatic β-cells, floxed alleles of Men1 were selectively ablated using Cre-recombinase driven by the insulin promoter. Despite the β-cell specificity of the RipCre, glucagon-expressing tumors as well as insulinomas developed in old mutant mice. These glucagon-expressing tumor cells were menin deficient and expressed the mature α-cell-specific transcription factors Brain-specific homeobox POU domain protein 4 (Brn4) and v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (MafB). Moreover, the inactivation of β-cell-specific transcription factors was observed in mutant β-cells. Our work shows that Men1 ablation in the pancreatic β-cells leads to the inactivation of specific transcription factors, resulting in glucagon-expressing tumor development, which sheds light on the mechanisms of islet tumorigenesis.
authors.affiliation: Department of Endocrinology and Metabolism (F.L., Y.S., Y.Ch., X.J., Y.P., Y.L., J.L., Y.G., Y.Ca., W.W., G.N.), Shanghai Clinical Center for Endocrine and Metabolic Diseases and Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, and Laboratory of Endocrinology and Metabolism (G.N.), Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; and Laboratoire Génétique Moléculaire, Signalisation et Cancer (C.Z.), Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5201, Faculté de Médecine, Université Claude Bernard Lyon, Centre Leon-Berard, Lyon69366, France.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Yutong
authors.initials: Y
authors.lastname: Su
authors.forename: Yulong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Xiuli
authors.initials: X
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.forename: Jieli
authors.initials: J
authors.lastname: Lu
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Gu
authors.forename: Changxian
authors.initials: C
authors.lastname: Zhang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cao
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D000818:Animals; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005838:Genotype; D005934:Glucagon / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000502:physiology; D005935:Glucagonoma / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D014157:Transcription Factors
chemical_list: C484898:Men1 protein, mouse; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D005934:Glucagon