title: Islet cell hyperplasia in transgenic mice overexpressing EAT/mcl-1, a bcl-2 related gene.
abstract: EAT/mcl-1 (EAT), a bcl-2 related anti-apoptotic gene, is up-regulated at the early stage of differentiation of human embryonal carcinoma cells; cells which serve as a model for early embryogenesis. We generated transgenic mice for the human EAT gene driven by the EF1 alpha promoter in order to elucidate its functional role in vivo. Histologically, these mice exhibited hyperplasia of Langerhans islet cells; pancreatic cell regions composed of both insulin- and glucagon-producing cells. Furthermore, Bax and Bag-1 -- possible heterodimeric partners for EAT in the anti-apoptotic process -- were up-regulated in islets isolated from the EAT transgenic mice. The insulin tolerance test exhibited no significant difference between the EAT transgenic mice and non-transgenic mice, indicating that islet cell hyperplasia was not due to insulin resistance. In conclusion, EAT transgenic mice exhibit hyperplasia of pancreatic beta cells. EAT may inhibit apoptosis of beta cells, allowing these cells to circumvent the process of apoptosis until the adult stage.
authors.affiliation: Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsushita
authors.forename: Hajime
authors.initials: H
authors.lastname: Okita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Kouji
authors.initials: K
authors.lastname: Shimoda
authors.forename: Mariko
authors.initials: M
authors.lastname: Fukuma
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Urano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Honda
authors.forename: Makoto
authors.initials: M
authors.lastname: Sano
authors.forename: Shiro
authors.initials: S
authors.lastname: Iwanaga
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hata
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
mesh_terms: D007516:Adenoma, Islet Cell / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D048429:Cell Size; D019254:Genes, bcl-2; D006801:Humans; D006965:Hyperplasia / Q000209:etiology* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2
chemical_list: D007328:Insulin; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2