A SIMIAN-VIRUS-40 LARGE T-ANTIGEN SEGMENT CONTAINING AMINO-ACIDS 1 TO127 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 o f tissues in transgenic mice, the precise tissues depending on the tis sue specificity of the upstream region controlling T-antigen expressio n. Expression of mutant T antigens that contain a subset of the protei n'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 i nstances, the alteration in tumor induction or progression correlated with inability of the mutant large T antigen to bind the tumor suppres sor p53. In the study reported here, we investigated the capacity of a n N-terminal T antigen segment (T1-127) expressed in conjunction with small t antigen under control of the rat elastase-l (El) promoter to i nduce pancreatic tumors, The results show that pancreases of transgeni c mice expressing T1-127 and small t antigen display acinar cell dyspl asia at birth that progresses to neoplasia, The average age to death i n these mice is within the range reported for transgenic mice expressi ng full-length T antigen under control of the El promoter, These resul ts indicate that sequestering p53 by binding is not required for the d evelopment of rapidly growing acinar cell carcinomas, In addition, we provide evidence that small t antigen is unlikely to be required, Fina lly, we show that the p53 protein in acinar cell carcinomas is wild ty pe in conformation.