Multiple polypeptide hormone expression in pancreatic islet cell carcinomas derived from phosphoenolpyruvatecarboxykinase-SV40 T antigen transgenic rats

Transgenic rats carrying a PEPCK-SV40 large T-antigen (TAg) transgene rapid ly develop numerous pancreatic islet cell neoplasms, the cells of which exp ress TAg. Although many of the larger neoplasms contain relatively undiffer entiated cells, many tumors contain areas of well-differentiated cells with abundant endoplasmic reticulum (ER) and secretory granules for endocrine h ormones like those observed in normal pancreatic islets. In the well-differ entiated lesions. glucagon-producing alpha-cells, insulin-producing beta-ce lls, and somatostatin-producing delta-cells are readily identifiable morpho logically under the electron microscope. beta-cells were observed in all no rmal and hyperplastic islets, and nests of these cells were scattered throu ghout the larger neoplasms. These nests varied from small clusters of epith elium-like cells that stain intensely for insulin, to sheets of small, baso philic cells that stain more diffusely for the hormone. alpha-Cells were al so present in all of the normal and hyperplastic islets, bur in larger hype rplastic islets, the peripheral localization was absent. Larger neoplasms c ontained many nests of glucagon-expressing cells, as well as scattered gluc agon-producing single cells, delta-Cells were rarely observed in the hyperp lastic islets and in the neoplasms. Blood glucose levels were unaltered in the transgenic animals relative to their nontransgenic litter mates. Thus a lthough these islet cell neoplasms express several polypeptide hormones, th ere is no obvious clinical effect of such expression in vivo.