Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AR42J is an exocrine pancreatic cell line that has been reported to differentiate towards an endocrine phenotype when stimulated with various growth factors, such as activin A, hepatocyte growth factor (HGF), betacellulin or glucagon-like peptide 1. In our experiments, AR42J-B13 cells differentiated morphologically in response to the growth factor treatment as reported previously. However, they failed to express the insulin gene. We found that the cells did not express several transcription factors known to be found in the beta-cell, including Nkx6.1, isl-1, Pax4 and Pax6. In addition, the mRNA level for pdx-1 and Nkx2.2 were very low in comparison to the insulinoma cell lines INS-1 and RINm5F. However, some transcription factors typically found in beta-cells and neuroendocrine cells were expressed also in the AR42J-B13 cells. These included BETA2/NeuroD, HNF1alpha, C/EBPbeta and IA-1. Unlike the insulinoma cells, AR42J cells expressed the exocrine transcription factor p48. In order to induce endocrine differentiation, we transfected the AR42J-B13 cells with the full length cDNAs of isl-1, Nkx6.1, Nkx2.2 and pdx-1 under the control of the CMV promoter, both separately and in combinations. The expression of Nkx2.2 led consistently to the appearance of pancreatic polypeptide but not insulin, glucagon or somatostatin mRNA. The PP mRNA expression in Nkx2.2 cDNA transfected cells was independent of the growth factor treatment used for differentiating AR42J cells. In conclusion, the AR42J-B13 line possesses some features of a pancreatic neuroendocrine cell. However, we were unable to confirm the capacity of these cells to differentiate into insulin-producing cells. Our results indicate that Nkx2.2 plays a role in the transcriptional regulation of PP expression.
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PMID:Transcription factor expression and hormone production in pancreatic AR42J cells. 1094 Apr 82

During pancreatic development, the paired homeodomain transcription factor PAX4 is required for the differentiation of the insulin-producing beta cells and somatostatin-producing delta cells. To establish the position of PAX4 in the hierarchy of factors controlling islet cell development, we examined the control of the human PAX4 gene promoter. In both cell lines and transgenic animals, a 4.9-kilobase pair region directly upstream of the human PAX4 gene transcriptional start site acts as a potent pancreas-specific promoter. Deletion mapping experiments demonstrate that a 118-base pair region lying approximately 1.9 kilobase pairs upstream of the transcription start site is both necessary and sufficient to direct pancreas-specific expression. Serial deletions through this region reveal the presence of positive elements that bind several pancreatic transcription factors as follows: the POU homeodomain factor HNF1alpha, the orphan nuclear receptor HNF4alpha, the homeodomain factor PDX1, and a heterodimer composed of two basic helix-loop-helix factors. Interestingly, mutations in the genes encoding four of these factors cause a dominantly inherited form of human diabetes called Maturity Onset Diabetes of the Young. In addition, PAX4 itself has at least two high affinity binding sites within the promoter through which it exerts a strong negative autoregulatory effect. Together, these results suggest a model in which PAX4 expression is activated during pancreatic development by a combination of pancreas-specific factors but is then switched off once PAX4 protein reaches sufficient levels.
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PMID:Autoregulation and maturity onset diabetes of the young transcription factors control the human PAX4 promoter. 1096 7

During fetal development, paired/homeodomain transcription factor Pax4 controls the formation of the insulin-producing beta cells and the somatostatin-producing delta cells in the islets of Langerhans in the pancreas. Targeting of Pax4 expression to the islet lineage in the fetal pancreas depends on a short sequence located approximately 2 kb upstream of the transcription initiation site of the PAX4 gene. This short sequence contains binding sites for homeodomain transcription factors PDX1 and hepatic nuclear factor (HNF)1, nuclear receptor HNF4alpha, and basic helix-loop-helix factor Neurogenin3. In the current study we demonstrate that the HNF1alpha and Neurogenin3 binding sites are critical for activity of the region through synergy between the two proteins. Synergy involves a physical interaction between the factors and requires the activation domains of both factors. Furthermore, exogenous expression of Neurogenin3 is sufficient to induce expression of the endogenous pax4 gene in the mouse pancreatic ductal cell line mPAC, which already expresses HNF1alpha, whereas expression of both Neurogenin3 and HNF1alpha are necessary to activate the pax4 gene in the fibroblast cell line NIH3T3. These data demonstrate how Neurogenin3 and HNF1alpha activate the pax4 gene during the cascade of gene expression events that control pancreatic endocrine cell development.
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PMID:Neurogenin3 and hepatic nuclear factor 1 cooperate in activating pancreatic expression of Pax4. 1283 60