title: 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.
authors.affiliation: Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109-2200, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Else
authors.forename: Alessia
authors.initials: A
authors.lastname: Trovato
authors.forename: Alex C
authors.initials: AC
authors.lastname: Kim
authors.forename: Yipin
authors.initials: Y
authors.lastname: Wu
authors.forename: David O
authors.initials: DO
authors.lastname: Ferguson
authors.forename: Rork D
authors.initials: RD
authors.lastname: Kuick
authors.forename: Peter C
authors.initials: PC
authors.lastname: Lucas
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hammer
mesh_terms: D000302:Adrenal Cortex / Q000002:abnormalities* / Q000378:metabolism; D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D043171:Chromosomal Instability / Q000235:genetics / Q000502:physiology; D005260:Female; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010641:Phenotype; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology; D012880:Skin Pigmentation / Q000235:genetics / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics / Q000502:physiology; D016615:Telomere / Q000235:genetics / Q000502:physiology; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000502:physiology*; D013737:Testis / Q000473:pathology / Q000503:physiopathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000502:physiology*
chemical_list: C544060:Acd protein, mouse; D034501:Telomere-Binding Proteins; D016159:Tumor Suppressor Protein p53