A simian virus 40 large T-antigen segment containing amino acids 1 to 127 and expressed under the control of the rat elastase-1 promoter produces pancreatic acinar carcinomas in transgenic mice.
The simian virus 40 large T antigen induces tumors in a wide variety of tissues in transgenic mice, the precise tissues depending on the tissue specificity of the upstream region controlling T-antigen expression. Expression of mutant T antigens that contain a subset of the protein's activities restricts the spectrum of tumors induced. Others showed previously that expression of a mutant large T antigen containing the N-terminal 121 amino acids (T1-121) under control of the lymphotropic papovavirus promoter resulted in slow-growing choroid plexus tumors, whereas full-length T antigen under the same promoter induced rapidly growing CPR tumors, T-cell lymphomas, and B-cell lymphomas. In those instances, the alteration in tumor induction or progression correlated with inability of the mutant large T antigen to bind the tumor suppressor p53. In the study reported here, we investigated the capacity of an N-terminal T antigen segment (T1-127) expressed in conjunction with small t antigen under control of the rat elastase-1 (E1) promoter to induce pancreatic tumors. The results show that pancreases of transgenic mice expressing T1-127 and small t antigen display acinar cell dysplasia at birth that progresses to neoplasia. The average age to death in these mice is within the range reported for transgenic mice expressing full-length T antigen under control of the E1 promoter. These results indicate that sequestering p53 by binding is not required for the development of rapidly growing acinar cell carcinomas. In addition, we provide evidence that small t antigen is unlikely to be required. Finally, we show that the p53 protein in acinar cell carcinomas is wild type in conformation.
Tevethia
M J
MJ
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Bonneau
R H
RH
Griffith
J W
JW
Mylin
L
L
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D018267:Carcinoma, Acinar Cell / Q000473:pathology / Q000821:virology*; D016158:Genes, p53; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010196:Pancreatic Elastase / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000821:virology*; D011401:Promoter Regions, Genetic
D000952:Antigens, Polyomavirus Transforming; D010196:Pancreatic Elastase