[PDF][PDF] Genetic p53 deficiency partially rescues the adrenocortical dysplasia phenotype at the expense of increased tumorigenesis

T Else, A Trovato, AC Kim, Y Wu, DO Ferguson… - Cancer Cell, 2009 - cell.com
T Else, A Trovato, AC Kim, Y Wu, DO Ferguson, RD Kuick, PC Lucas, GD Hammer
Cancer Cell, 2009cell.com
Telomere dysfunction and shortening induce chromosomal instability and tumorigenesis. In
this study, we analyze the adrenocortical dysplasia (acd) mouse, harboring a mutation in
Tpp1/Acd. Additional loss of p53 dramatically rescues the acd phenotype in an organ-
specific manner, including skin hyperpigmentation and adrenal morphology, but not germ
cell atrophy. Survival to weaning age is significantly increased in Acd acd/acd p53−/− mice.
On the contrary, p53−/− and p53+/− mice with the Acd acd/acd genotype show a decreased …
Summary
Telomere dysfunction and shortening induce chromosomal instability and tumorigenesis. In this study, we analyze the adrenocortical dysplasia (acd) mouse, harboring a mutation in Tpp1/Acd. Additional loss of p53 dramatically rescues the acd phenotype in an organ-specific manner, including skin hyperpigmentation and adrenal morphology, but not germ cell atrophy. Survival to weaning age is significantly increased in Acdacd/acd p53−/− mice. On the contrary, p53−/− and p53+/− mice with the Acdacd/acd genotype show a decreased tumor-free survival, compared with Acd+/+ mice. Tumors from Acdacd/acd p53+/− mice show a striking switch from the classic spectrum of p53−/− mice toward carcinomas. The acd mouse model provides further support for an in vivo role of telomere deprotection in tumorigenesis.
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