Changes in the expression of transcription factors in pancreatic AR42J cells during differentiation into insulin-producing cells.
Pancreatic AR42J cells possess both exocrine and neuroendocrine properties and convert to insulin-producing cells upon treatment with activin A and hepatocyte growth factor (HGF). We studied changes in the mRNA expression of various transcription factors during the course of differentiation. Among the transcription factors studied, expression levels of Pax4 and neurogenin3 changed significantly. These two factors were not detected in naive cells, whereas their mRNA levels were markedly increased after treatment with activin A and HGF. Thus, these two factors were induced by activin A. Transfection of Pax4 did not induce any changes in morphology or expression of pancreatic polypeptide (PP). Furthermore, introduction of antisense Pax4 did not affect the conversion into insulin-producing cells induced by activin A and HGF. In contrast, transfection of neurogenin3 induced morphological changes similar to those induced by activin A. In addition, transfection of neurogenin3 induced the expression of PP. Conversely, introduction of antisense neurogenin3 blocked the differentiation of AR42J cells induced by activin A and HGF. These results indicate that activin A regulates the expression of neurogenin3, which is critical for the differentiation of AR42J into endocrine cells.
Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
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Zhang
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Mashima
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Kojima
D028341:Activins; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D016373:DNA, Antisense / Q000235:genetics; D004274:DNA, Recombinant; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007265:Inhibins / Q000494:pharmacology; D007328:Insulin / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics; D051761:Paired Box Transcription Factors; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D028341:Activins; D051792:Basic Helix-Loop-Helix Proteins; D016373:DNA, Antisense; D004274:DNA, Recombinant; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; D018398:Homeodomain Proteins; D007265:Inhibins; D007328:Insulin; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C498695:NEUROG3 protein, human; C491709:PAX4 protein, human