Role of the amino-terminal domain of simian virus 40 early region in inducing tumors in secretin-expressing cells in transgenic mice.
OBJECTIVE
The early region of simian virus 40 (SV40) encodes 2 transforming proteins, large T (Tag) and small t antigen, that produce neuroendocrine tumors in the intestine and the pancreas when expressed in secretin cells of transgenic mice.


METHODS
Two SV40 early-region transgenes containing a deletion that eliminated expression of the small t antigen were expressed in transgenic mice under control of the secretin gene. The 2 lines of mice, one expressing the native large T antigen and the other T antigen with a mutation in its N-terminal J domain, were examined to determine which biological activities of the SV40 early region were required for tumorigenesis.


RESULTS
Most animals expressing wild-type large T antigen developed pancreatic insulinomas and lymphomas and died between 3 and 6 months of age. However, small intestinal neoplasms were extremely rare in the absence of small t antigen expression. Transgenic lines expressing the J domain mutant failed to develop tumors.


CONCLUSIONS
Transformation of secretin-producing enteroendocrine cells by SV40 requires functional cooperation between intact large T and small t oncoproteins. In contrast, large T antigen alone is sufficient to induce tumors in the endocrine pancreas and thymus.
Ratineau
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C
Division of Gastroenterology and GRASP Digestive Disease Center, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Ronco
A
A
Leiter
A B
AB
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics; D007340:Insulinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D019683:Penetrance; D012633:Secretin / Q000378:metabolism*; D013539:Simian virus 40 / Q000235:genetics* / Q000502:physiology*
D000957:Antigens, Viral, Tumor; D012633:Secretin