Development of neuroendocrine tumors in the gastrointestinal tract of transgenic mice. Heterogeneity of hormone expression

Rindi, G., Grant, S. G., Yiangou, Y., Ghatei, M. A., Bloom, S. R., Bautch, V. L., Solcia, E., Polak, J. M. (June 1990) Development of neuroendocrine tumors in the gastrointestinal tract of transgenic mice. Heterogeneity of hormone expression. Am J Pathol, 136 (6). pp. 1349-63. ISSN 0002-9440 (Print)0002-9440 (Linking)



Expression of hormones in endocrine tumors and derived cell lines of transgenic mice carrying insulin-promoted oncogenes has been investigated by histochemical, immunohistochemical, ultrastructural, and radioimmunologic means. Tumors of the pancreas, small intestine, mesentery, and liver were examined. Insulin-immunoreactive cells were prevalent in pancreatic tumors, with a significant subpopulation of pancreatic polypeptide-immunoreactive elements. Conventional ultrastructural and immunogold analysis identified insulin-storing beta granules in pancreatic tumor cells. In contrast, the largest immunoreactive subpopulation of intestinal tumors expressed secretin (53% of total cells), followed by proglucagon-related peptides (15%), glucose-dependent insulinotropic polypeptide (7%), gastrin (7%), pancreatic polypeptide (2%), neurotensin (2%), and somatostatin (1%). No detectable immunoreactivity for either insulin or serotonin was observed. Electron microscopy and immunogold labeling showed that intestinal tumor cells contained secretin-storing S-type granules. Lymph node and liver tumors contained secretin-immunoreactive cells with ultrastructural features similar to those of intestinal tumors. In addition, high levels of circulating insulinlike and secretinlike immunoreactants were detectable. Analogous hormone profiles were identified in tumor cell lines and culture media. Large T-antigen immunoreactivity was detected in all the nuclei of neoplastic cells, as well as in insulin-immunoreactive elements of non-neoplastic islets and pancreatic ducts and in some secretin-immunoreactive cells of small intestinal mucosa. These data indicate that neuroendocrine tumors arise both in beta cell and S-cell subpopulations of transgenic mice.

Item Type: Paper
Uncontrolled Keywords: Animals Disease Models, Animal Endocrine Glands/metabolism/pathology/ultrastructure Endocrine System Diseases/metabolism/*pathology Gastrointestinal Neoplasms/metabolism/*pathology/ultrastructure Gene Expression Immunohistochemistry Insulin/blood/genetics/metabolism Intestinal Neoplasms/metabolism/pathology/ultrastructure Liver Neoplasms/metabolism/pathology/ultrastructure Lymphoma/metabolism/pathology/ultrastructure Mice Mice, Transgenic Microscopy, Electron Neoplasms, Experimental/metabolism/*pathology/ultrastructure Pancreatic Neoplasms/metabolism/pathology/ultrastructure Promoter Regions, Genetic Radioimmunoassay Secretin/blood/metabolism Simian virus 40/genetics Time Factors Tumor Cells, Cultured/metabolism/pathology/ultrastructure
Subjects: diseases & disorders > cancer
diseases & disorders > endocrine system diseases
CSHL Authors:
Communities: CSHL labs
Depositing User: Matt Covey
Date: June 1990
Date Deposited: 04 Apr 2016 20:31
Last Modified: 04 Apr 2016 20:31
PMCID: PMC1877573

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