Universität zu Köln

Gottlieb, Aline, Althoff, Kristina, Grunewald, Laura, Thor, Theresa, Odersky, Andrea, Schulte, Marc, Deubzer, Hedwig E., Heukamp, Lukas ORCID: 0000-0002-3388-3482, Eggert, Angelika, Schramm, Alexander ORCID: 0000-0001-7670-7529, Schulte, Johannes H. and Kuenkele, Annette (2017). RITA displays anti-tumor activity in medulloblastomas independent of TP53 status. Oncotarget, 8 (17). S. 27882 - 27892. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

Current therapy of medulloblastoma, the most common malignant brain tumor of childhood, achieves 40-70% survival. Secondary chemotherapy resistance contributes to treatment failure, where TP53 pathway dysfunction plays a key role. MDM2 interaction with TP53 leads to its degradation. Reactivating TP53 functionality using small-molecule inhibitors, such as RITA, to disrupt TP53-MDM2 binding may have therapeutic potential. We show here that RITA decreased viability of all 4 analyzed medulloblastoma cell lines, regardless of TP53 functional status. The decrease in cell viability was accompanied in 3 of the 4 medulloblastoma cell lines by accumulation of TP53 protein in the cells and increased CDKN1A expression. RITA treatment in mouse models inhibited medulloblastoma xenograft tumor growth. These data demonstrate that RITA treatment reduces medulloblastoma cell viability in both in vitro and in vivo models, and acts independently of cellular TP53 status, identifying RITA as a potential therapeutic agent to treat medulloblastoma.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gottlieb, Aline UNSPECIFIED UNSPECIFIED UNSPECIFIED Althoff, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Grunewald, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Thor, Theresa UNSPECIFIED UNSPECIFIED UNSPECIFIED Odersky, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulte, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Deubzer, Hedwig E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heukamp, Lukas UNSPECIFIED orcid.org/0000-0002-3388-3482 UNSPECIFIED Eggert, Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED Schramm, Alexander UNSPECIFIED orcid.org/0000-0001-7670-7529 UNSPECIFIED Schulte, Johannes H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuenkele, Annette UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-233714
DOI:	10.18632/oncotarget.15840
Journal or Publication Title:	Oncotarget
Volume:	8
Number:	17
Page Range:	S. 27882 - 27892
Date:	2017
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SMALL-MOLECULE RITA; P53 FUNCTION; CURRENT CONSENSUS; BRAIN-TUMORS; MUTANT P53; IN-VITRO; APOPTOSIS; CELLS; ACTIVATION; CHILDHOOD Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23371