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Genetic p53 deficiency partially rescues the adrenocortical dysplasia phenotype at the expense of increased tumorigenesis.

ABSTRACT: 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 tumor-free survival, compared with Acd(+/+) mice. Tumors from Acd(acd/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.

SUBMITTER: Else T

PROVIDER: S-EPMC2703790 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Genetic p53 deficiency partially rescues the adrenocortical dysplasia phenotype at the expense of increased tumorigenesis.

Else Tobias T Trovato Alessia A Kim Alex C AC Wu Yipin Y Ferguson David O DO Kuick Rork D RD Lucas Peter C PC Hammer Gary D GD

Cancer cell 20090601 6

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 Ac ...[more]

PMID: 19477426

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