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Reduced Tumorigenicity of Mouse ES Cells and the Augmented Anti-Tumor Therapeutic Effects under Parg Deficiency


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Title: Reduced Tumorigenicity of Mouse ES Cells and the Augmented Anti-Tumor Therapeutic Effects under Parg Deficiency
Authors: Sonoda, Yuki / Sasaki, Yuka / Gunji, Akemi / Shirai, Hidenori / Araki, Tomonori / Imamichi, Shoji / Onodera, Takae / Rydén, Anna-Margareta / Watanabe, Masatoshi / Itami, Jun / Honda, Takuya / Ashizawa, Kazuto / Nakao, Kazuhiko / Masutani, Mitsuko
Issue Date: 24-Apr-2020
Publisher: MDPI
Citation: Cancers, 12(4), art.no.1056; 2020
Abstract: PolyADP-ribosylation is a post-translational modification of proteins, and poly(ADP-ribose) (PAR) polymerase (PARP) family proteins synthesize PAR using NAD as a substrate. Poly(ADP-ribose) glycohydrolase (PARG) functions as the main enzyme for the degradation of PAR. In this study, we investigated the effects of Parg deficiency on tumorigenesis and therapeutic efficacy of DNA damaging agents, using mouse ES cell-derived tumor models. To examine the effects of Parg deficiency on tumorigenesis, Parg+/+ and Parg−/− ES cells were subcutaneously injected into nude mice. The results showed that Parg deficiency delays early onset of tumorigenesis from ES cells. All the tumors were phenotypically similar to teratocarcinoma and microscopic findings indicated that differentiation spectrum was similar between the Parg genotypes. The augmented anti-tumor therapeutic effects of X-irradiation were observed under Parg deficiency. These results suggest that Parg deficiency suppresses early stages of tumorigenesis and that Parg inhibition, in combination with DNA damaging agents, may efficiently control tumor growth in particular types of germ cell tumors
Keywords: Cancer / ES cells / Poly(ADP-ribose) glycohydrolase / Poly(ADP-ribose) polymerase / Radiosensitization
URI: http://hdl.handle.net/10069/39986
DOI: 10.3390/cancers12041056
Rights: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/39986

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