Abstract
Tumor induction with MCA was followed in transgenic mice with mutated p53 gene carrying a 9 bp deletion in exon 6. The mutated p53 cDNA was obtained from radiation-induced mouse tumors and ligated to the expression vector pCXN2. The construct, pTE50, was introduced into mouse embryos to generate pTE50(+/-) mice. The mice were injected subcutaneously with 0.02 mg MCA dissolved in olive oil. Tumor incidence by May 2006 was 64% (32/52) in pTE50 (+/-) mice and 41 % (20/49) in wild-type mice, indicating a substantial increase in tumor incidence (p<0.05). Treatment of autochthonous MCA-induced tumors of 5 mm in diameter with siRNA, that was designed from the promoter sequence and was confirmed to suppress the expression of the mutated p53 mRNA, was effective in yielding a complete cure in 2 and growth inhibition in 2 out of 17 in pTE50(+/-) mice, while for tumors in wild-type mice, siRNA was not effective in all 4 cases. For transplanted pTE50(+/-) tumors of the MCA-induced origin, siRNA treatment yielded a complete cure in 2 and growth inhibition in 3 out of 14 cases, while for transplanted wild-type tumors, siRNA was ineffective in all of 3 cases.
