A tumour model for the study of islet cell differentiation

Madsen, Ole; Serup, Palle; Karlsen, Christina; Lund, Kaare; Petersen, Helle V.; Blume, Niels; Andersen, Frank G.; Jensen, Jan; Michelsen, Birgitte

doi:10.1042/bst0210142

Cited by 5 publications

(1 citation statement)

References 7 publications

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“…Based on immunohistochemical analysis of hormone expression in the developing pancreas (5,6) and the multihormonal phenotype of most pancreatic endocrine tumors (7,8), we and others have previously suggested that the -c e l l originates from early multihormonal precursor cells. It was thought that all of the islet endocrine cells would be related in a direct lineage relationship.…”

Section: Rapid Publicationmentioning

confidence: 99%

Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation.

Jensen¹,

Heller²,

et al. 2000

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The nature and identity of the pancreatic -cell precursor has remained elusive for many years. One model envisions an early multihormonal precursor that gives rise to both -and -cells and the other endocrine cell types. Alternatively, -cells have been suggested to arise late, directly from the GLUT2-and pancreatic duodenal homeobox factor-1 (PDX1)-expressing epithelium, which gives rise also to the acinar cells during this stage. In this study, we have identified a subset of the PDX1 + epithelial cells that are marked by expression of N e u r o g e n i n 3 (N g n 3 ). N g n 3 , a member of the basic helix-loop-helix (

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Section: Rapid Publicationmentioning

confidence: 99%

Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation.

Jensen¹,

Heller²,

et al. 2000

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Pax4 Represses Pancreatic Glucagon Gene Expression

Petersen

Jørgensen

Andersen

et al. 2000

Molecular Cell Biology Research Communications

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Islet expression of Rhombotin and Isl-1 suggests cell type specific exposure of LIM-domain epitopes

Lund¹,

Petersen²,

Jensen³

et al. 1995

Endocr

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The homeodomain protein Isl-1 and the proto-oncogene Rhombotin (a LIM-only protein), share a double zinc-binding LIM domain and have both been implicated in neural and possibly endocrine development. Isl-1 is expressed in all endocrine cell-types of the islet of Langerhans while Rhombotin mRNA expression was reported in rat insulinoma cells. We have cloned and sequenced Rhombotin cDNA from rat insulinoma (99.4% identical to human and mouse sequences) and demonstrate that it is expressed in normal islets, intestinal tissue, and testis, in addition to the brain; but absent in all other organs tested. Rhombotin mRNA is expressed in phenotypically distinct islet tumours (α-, β, and δ-tumours) at levels comparable to that of normal islets. Antisera raised against two distinct epitopes contained within a short synthetic peptide representing part of the N-terminal LIM domain of Rhombotin surprisingly stain α- and δ-cells, respectively, on sections of rat pancreas. Rhombotin is undetectable by immunocytochemistry using LIM-domain antisera on intact monolayer islet tumor cells or transfected fibroblasts while readily detectable when equipped with a FLAG epitope, as detected with FLAG antiserum. In contrast, recombinant FLAG-Rhombotin is efficiently recognised by Western blotting or immunoprecipitation with all LIM-specific antisera. Almost identical results were obtained with LIM-specific versus homeodomain/C-terminal Isl-1 antisera staining α-cell cytoplasm or all islet nuclei, respectively. We conclude that Rhombotin in addition to Isl-1 is expressed in the islet of Langerhans and propose that the differential staining patterns obtained with antisera towards the LIM domains versus flanking epitopes of both proteins reflect (1) cell-specific protein-protein interactions of these domains or, alternatively, (2) islet cell type specific expression of novel homologous LIM domain proteins.

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A tumour model for the study of islet cell differentiation

Cited by 5 publications

References 7 publications

Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation.

Independent development of pancreatic alpha- and beta-cells from neurogenin3-expressing precursors: a role for the notch pathway in repression of premature differentiation.

Pax4 Represses Pancreatic Glucagon Gene Expression

Islet expression of Rhombotin and Isl-1 suggests cell type specific exposure of LIM-domain epitopes

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