5'-AZA induces Ngn3 expression and endocrine differentiation in the PANC-1 human ductal cell line.
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.
Lefebvre
Bruno
B
Univ Lille Nord de France, F-59000 Lille, France. bruno.lefebvre@inserm.fr
Belaich
Sandrine
S
Longue
Justine
J
Vandewalle
Brigitte
B
Oberholzer
Jose
J
Gmyr
Valery
V
Pattou
François
F
Kerr-Conte
Julie
J
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
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