Expression of a novel zinc-finger cDNA, IA-1, is associated with rat AR42J cells differentiation into insulin-positive cells.
BACKGROUND
IA-1, an insulinoma-associated cDNA-1, encodes a zinc-finger DNA-binding protein originally isolated from a human insulinoma subtraction library.


OBJECTIVE
To demonstrate the restriction of IA-1 gene expression in human fetal pancreata of different gestational stages and to determine whether the expression of IA-1 gene is associated with rat AR42J cell differentiation into insulin-positive cells.


METHODS
To examine whether the IA-1 gene is associated with pancreatic endocrine cell differentiation, we used a rat pancreatic amphicrine cell line, AR42J, to investigate whether the expression of the IA-1 gene coincides with AR42J cells converting into either endocrine or exocrine lineage. We also examined a set of islet transcription factors that regulate key differentiation steps involved in activating the genes that confer the specialized functions of terminally differentiated pancreatic islet cells.


RESULTS
When the AR42J cells were converted into insulin-positive cells induced by GLP-1, insulinoma conditioned-medium, or both, we observed a significant elevated expression of mRNA for IA-1 and islet-specific transcription factors such as Pdx-1, NeuroD/beta2, and Nkx6.1. In contrast, dramatically decreased expression of mRNA for IA-1 and islet-specific transcription factors was displayed when AR42J cells were converted into the acinar-like phenotype by dexamethasone.


CONCLUSIONS
IA-1 gene was shown to be developmentally regulated in fetal pancreatic cells, and its expression pattern is consistent with parallel changes in islet-specific transcription factors during the endocrine differentiation of AR42J cells.
Zhu
Min
M
Research Institute for Children, Children's Hospital, 520 Elmwood Park Blvd., Harahan, Louisiana 70123, U.S.A.
Breslin
Mary B
MB
Lan
Michael S
MS
D000328:Adult; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005333:Fetus / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005934:Glucagon / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007340:Insulinoma; D007515:Islets of Langerhans / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers / Q000235:genetics*
D051792:Basic Helix-Loop-Helix Proteins; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D018398:Homeodomain Proteins; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; C093970:NEUROD1 protein, human; C105201:NKX6-1 protein, human; C501008:Neurod1 protein, mouse; C491328:Nkx6-1 protein, mouse; C491327:Nkx6-1 protein, rat; C084010:pancreatic and duodenal homeobox 1 protein; C087342:INSM1 protein, human