title: 5'-AZA induces Ngn3 expression and endocrine differentiation in the PANC-1 human ductal cell line.
abstract: Neurogenin 3 is necessary for endocrine cell development in the embryonic pancreas and has been shown to induce transdifferentiation duct cells from adult pancreas toward a neuro-endocrine phenotype. Here we discovered that the demethylating agent 5'-Azadeoxycytidine (AZA) induced Ngn3 expression and endocrine differentiation from the PANC-1 human ductal cell line. The expression of markers specific to mature islet cells, i.e., glucagon and somatostatin, was also observed. In addition, we demonstrated that growth factors (betacellulin and soluble factors released during pancreas embryogenesis) increased the level of maturation. Our studies revealed that the PANC-1 model system may provide a basis for elucidating the ductal/endocrine differentiation.
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France. bruno.lefebvre@inserm.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Lefebvre
authors.forename: Sandrine
authors.initials: S
authors.lastname: Belaich
authors.forename: Justine
authors.initials: J
authors.lastname: Longue
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vandewalle
authors.forename: Jose
authors.initials: J
authors.lastname: Oberholzer
authors.forename: Valery
authors.initials: V
authors.lastname: Gmyr
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Julie
authors.initials: J
authors.lastname: Kerr-Conte
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis*; D002454:Cell Differentiation; D002460:Cell Line; D054338:Cell Transdifferentiation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: D001374:Azacitidine; D051792:Basic Helix-Loop-Helix Proteins; D015254:DNA Modification Methylases; D000077209:Decitabine; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C407737:Neurog3 protein, mouse