The Trp53 delta proline (Trp53ΔP) mouse exhibits increased genome instability and susceptibility to radiation‐induced, but not spontaneous, tumor development. Issue 9 (27th August 2015)

• Record Type: Journal Article
• Authors: Adams, Cassandra J.; Yu, Jennifer S.; Mao, Jian‐Hua; Jen, Kuang‐Yu; Costes, Sylvain V.; Wade, Mark; Shoemake, Jocelyn; Aina, Olulanu H.; Del Rosario, Reyno; Menchavez, Phuong Thuy; Cardiff, Robert D.; Wahl, Geoffrey M.; Balmain, Allan
• Is Part Of: Molecular carcinogenesis. Volume 55:Issue 9(2016:Sep.)
• Page Start: 1387
• Page End: 1396
• Publication Date: 2015-08-27
• Subjects: Trp53 -- cancer radiation -- genomic instability; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22377
• Languages: English
• ISSNs: 0899-1987

Abstract

Abstract : The tumor suppressor TP53 can initiate a plethora of anti‐proliferative effects to maintain genomic integrity under conditions of genotoxic stress. The N‐terminal proline‐rich domain (PRD) of TP53 is important in the regulation of TP53 activity and stability. A common polymorphism at codon 72 in this region has been associated with altered cancer risk in humans. The Trp53 ΔP mouse, which carries a germline homozygous deletion of a region of the PRD, does not develop spontaneous tumors in a mixed 129/Sv and C57BL/6 genetic background, but is highly susceptible to a broad range of tumor types following total body exposure to 4 Gy gamma (γ) radiation. This contrasts with the tumor spectrum in Trp53 null (−/−) mice, which mainly develop thymic lymphomas and osteosarcomas. Analysis of genomic instability in tissues and cells from Trp53 ΔP mice demonstrated elevated basal levels of aneuploidy, but this is not sufficient to drive spontaneous tumorigenesis, which requires an additional DNA damage stimulus. Levels of genomic instability did not increase significantly in Trp53 ΔP mice following irradiation exposure, suggesting that other radiation effects including tissue inflammation, altered metabolism or autophagy, may play an important role. The Trp53 ΔP mouse is a novel model to dissect the mechanisms of tumor development induced by radiation exposure. © 2015 Wiley Periodicals, Inc.