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Virchows Archiv

, Volume 427, Issue 6, pp 595–606 | Cite as

Development of colonic and pancreatic endocrine tumours in mice expressing a glucagon-SV40 T antigen transgene

  • S. L. Asa
  • Y. C. Lee
  • D. J. Drucker
Original Article

Abstract

We report the histological, immunohistochemical and ultrastructural changes in mice containing a chimeric glucagon-simian virus 40 T antigen (SV40Tag) gene. Transgene expression was detected in endocrine cells of pancreas, small and large intestine. Hyperplasia of glucagon-containing cells developed in pancreas and large bowel by gestational day 19. In large bowel, hyperplastic cells increased in number postnatally and invasive carcinomas were identified at 4 weeks; several animals had lymph node metastases. In contrast, no pathology was detected in the small bowel in any of the transgenic mice. Colonic tumours expressed SV40Tag, proglucagon-derived peptides and peptide YY (PYY); scattered cells contained cholecystokinin or glycoprotein hormone α-subunit. Somatostatin or serotonin was also detected in some tumours. By electron microscopy, the colonic tumours retained features of endocrine differentiation, but secretory granules were smaller than those of non-tumorous intestinal glucagon-producing L cells. In postnatal pancreas, atypical cells containing SV40Tag and glucagon were initially clustered at the periphery of islets; this atypical hyperplasia progressed to neoplasia by 11–12 weeks. Some neoplastic pancreatic cells contained glucagon, PYY or vasoactive intestinal peptide immunopositivity, but most were negative for all peptides; they contained immunoreactivity for tyrosine hydroxylase and by electron microscopy, pancreatic tumour cells had neuronal features. Pancreatic polypeptide was not detected in the non-tumorous islets of transgenic animals. This line of transgenic mice provides a model for the analysis of endocrine tumour progression in the gut and pancreas.

Key words

Transgenic mice Glucagon Colon carcinoma Pancreatic endocrine carcinoma Morphology 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • S. L. Asa
    • 1
  • Y. C. Lee
    • 2
    • 4
  • D. J. Drucker
    • 2
    • 3
  1. 1.Department of PathologyMount Sinai Hospital and the University of TorontoTorontoCanada
  2. 2.The Banting and Best Diabetes CenterUniversity of TorontoTorontoCanada
  3. 3.Departments of Medicine, Clinical Biochemistry and GeneticsThe Toronto HospitalTorontoCanada
  4. 4.Department of PhysiologyThe Chinese University of Hong KongHong Kong

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