Glucagonomas of transgenic mice express a wide range of general neuroendocrine markers and bioactive peptides

Rindi, G., Efrat, S., Ghatei, M. A., Bloom, S. R., Solcia, E., Polak, J. M. (1991) Glucagonomas of transgenic mice express a wide range of general neuroendocrine markers and bioactive peptides. Virchows Arch A Pathol Anat Histopathol, 419 (2). pp. 115-29. ISSN 0174-7398 (Print)0174-7398 (Linking)

DOI: 10.1007/BF01600225


Pancreatic tumours of transgenic mice carrying a glucagon-promoted simian virus 40 (SV40) T antigen oncogene have been analysed by histological, histochemical, ultrastructural and radioimmunological means. Seven transgenic mice were examined revealing dysplastic and neoplastic lesions in the endocrine pancreas. Four tumours were identified, one of which metastasized to periadrenal spaces and paravertebral lymph nodes. Benign tumours were composed of argyrophilic, endocrine cells reactive to a range of antibodies against neuroendocrine markers (neuron-specific enolase, protein gene product 9.5, chromogranin A, synaptophysin and protein 7B2) and different fragments of the proglucagon molecule (glucagon, glicentin, glucagon-like polypeptides 1 and 2). A few tumour cells expressed pancreatic polypeptide, somatostatin or insulin. Conventional ultrastructural analysis and immunogold labelling revealed typical glucagon-immunoreactive alpha granules which co-stored glicentin and glucagon-like polypeptides 1 and 2. The malignant primary tumour and its metastases were composed mainly of cells which did not show immunoreactivity for neuroendocrine markers or peptides. Atypical, glucagon-immunogold labelled granules were detected at electron microscopy in differentiated tumour cells and C-type retroviral particles in the largest tumour population of degranulated cells. The transgene-encoded oncoprotein SV40 large T-antigen was detected in the nuclei of well-differentiated tumour cells and in alpha cells of some dysplastic islets. All tumour-bearing mice showed high levels of circulating glucagon-like immunoreactivity. Transgenic mice harbouring the glucagon-promoted SV40 T antigen oncogene may provide a model for human glucagonoma.

Item Type: Paper
Uncontrolled Keywords: Animals Antigens, Polyomavirus Transforming/genetics Biological Markers Glucagon/analysis/genetics Glucagon-Like Peptide 1 Glucagonoma/genetics/metabolism/*pathology Immunohistochemistry Insulin/analysis Mice Mice, Transgenic Pancreatic Neoplasms/genetics/metabolism/*pathology Pancreatic Polypeptide/analysis Peptide Fragments/analysis Proglucagon Protein Precursors/analysis/genetics Radioimmunoassay Somatostatin/analysis
Subjects: organism description > animal > mammal > rodent > mouse
diseases & disorders > cancer > cancer types > pancreatic cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal
CSHL Authors:
Communities: CSHL labs > Wigler lab
Depositing User: Matt Covey
Date: 1991
Date Deposited: 07 Jan 2016 16:50
Last Modified: 07 Jan 2016 16:50
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