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p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

Wild, Peter J. and Ikenberg, Kristian and Fuchs, Thomas J. and Rechsteiner, Markus and Georgiev, Strahil and Fankhauser, Niklaus and Noske, Aurelia and Roessle, Matthias and Caduff, Rosmarie and Dellas, Athanassios and Fink, Daniel and Moch, Holger and Krek, Wilhelm and Frew, Ian J.. (2012) p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans. EMBO Molecular Medicine, 4. pp. 1-17.

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Official URL: http://edoc.unibas.ch/dok/A6008347

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Abstract

Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours.
Faculties and Departments:03 Faculty of Medicine
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Bereich Spezialfächer (Klinik) > Gynäkologie und Geburtshilfe
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Spezialfächer (Klinik) > Gynäkologie und Geburtshilfe
UniBasel Contributors:Dellas, Athanassios
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley-Blackwell
ISSN:1757-4676
e-ISSN:1757-4684
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:03 Oct 2017 08:45
Deposited On:14 Sep 2012 07:16

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