Increased tumor incidence and cure with siRNA in transgenic mice carrying radiation-induced mutant p53

Abstract

In the previous report, transgenic mice with mutant p53 from a radiation-induced mouse skin tumor showed a 1.7 fold elevated fibrosarcoma incidence as compared to wild type mice after subcutaneous injection of 3-methylcholanthrene. These tumors were suppressed by treatment with promoter-responsive siRNA #220 mixed with atelocollagen, with a frequency equivalent to the increased fraction of tumor incidence. Present report provides further characterization of the siRNA#220-responding tumor transplant line TT18. TT18 showed a drastic apoptosis and loss of the fibrous structure after treatment with siRNA#220 (0.0145 mg in 0.2ml; 2 applications with 2 day interval) along the time course of its regression from the size 5 mm diameter. When siRNA#220 was applied 2 days after TT18 transplantation at the right groin and negative control siRNA at the left groin, in the same mouse, tumor grew to 1.1 cm in diameter in 17 days at the left groin, while no tumor was formed in the right groin, indicating the effectiveness of local treatment with siRNA#220. These results show that the mutant p53 is indeed the cause of tumors and that these tumors can be cured by suppressing expression of the mutant p53.