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.