The role of SET/I2PP2A in canine mammary tumors

Abstract Canine mammary tumor is the most common neoplasm in female dogs, and it has generated considerable attention as a translational model for human breast cancer. Ser/Thr protein phosphatase 2A (PP2A) plays a critical role as a tumor suppressor, and SET/I2PP2A, the endogenous inhibitory protein...

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Autores principales:	Satoru Kake, Shunya Tsuji, Shuhei Enjoji, Sayaka Hanasaki, Hiroshi Hayase, Ryotaro Yabe, Yuiko Tanaka, Takayuki Nakagawa, Hao-Ping Liu, Shih-Chieh Chang, Tatsuya Usui, Takashi Ohama, Koichi Sato
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9d3996734a2e4ea98d3f019b4c72c5de
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spelling	oai:doaj.org-article:9d3996734a2e4ea98d3f019b4c72c5de2021-12-02T15:06:21ZThe role of SET/I2PP2A in canine mammary tumors10.1038/s41598-017-04291-72045-2322https://doaj.org/article/9d3996734a2e4ea98d3f019b4c72c5de2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04291-7https://doaj.org/toc/2045-2322Abstract Canine mammary tumor is the most common neoplasm in female dogs, and it has generated considerable attention as a translational model for human breast cancer. Ser/Thr protein phosphatase 2A (PP2A) plays a critical role as a tumor suppressor, and SET/I2PP2A, the endogenous inhibitory protein of PP2A, binds directly to PP2A and suppresses its phosphatase activity. Here, we investigated the role of SET in the tumorigenic growth in canine mammary tumor as well as in the sensitivity of tumors to existing therapeutics. Elevated protein levels of SET were observed in advanced-stage of canine mammary tumor tissues of dogs compared with paired normal tissues. Knockdown of SET expression in a canine mammary tumor cell line CIP-m led to increased PP2A activity and decreased cell proliferation, colony formation, and in vivo tumor growth. We observed suppression of mTOR, β-catenin, and NFκB signaling by SET knockdown. The sensitivity of CIP-m cells to doxorubicin was decreased by SET knockdown, while SET knockdown in CIP-m cells did not affect sensitivity to 4-OH-tamoxifen, carboplatin, bortezomib, and X-ray radiation. These data suggest that SET plays important roles in the tumor progression of a subset of canine mammary tumor by suppressing PP2A activity and enhancing mTOR, β-catenin, and NFκB signaling.Satoru KakeShunya TsujiShuhei EnjojiSayaka HanasakiHiroshi HayaseRyotaro YabeYuiko TanakaTakayuki NakagawaHao-Ping LiuShih-Chieh ChangTatsuya UsuiTakashi OhamaKoichi SatoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Satoru Kake Shunya Tsuji Shuhei Enjoji Sayaka Hanasaki Hiroshi Hayase Ryotaro Yabe Yuiko Tanaka Takayuki Nakagawa Hao-Ping Liu Shih-Chieh Chang Tatsuya Usui Takashi Ohama Koichi Sato The role of SET/I2PP2A in canine mammary tumors
description	Abstract Canine mammary tumor is the most common neoplasm in female dogs, and it has generated considerable attention as a translational model for human breast cancer. Ser/Thr protein phosphatase 2A (PP2A) plays a critical role as a tumor suppressor, and SET/I2PP2A, the endogenous inhibitory protein of PP2A, binds directly to PP2A and suppresses its phosphatase activity. Here, we investigated the role of SET in the tumorigenic growth in canine mammary tumor as well as in the sensitivity of tumors to existing therapeutics. Elevated protein levels of SET were observed in advanced-stage of canine mammary tumor tissues of dogs compared with paired normal tissues. Knockdown of SET expression in a canine mammary tumor cell line CIP-m led to increased PP2A activity and decreased cell proliferation, colony formation, and in vivo tumor growth. We observed suppression of mTOR, β-catenin, and NFκB signaling by SET knockdown. The sensitivity of CIP-m cells to doxorubicin was decreased by SET knockdown, while SET knockdown in CIP-m cells did not affect sensitivity to 4-OH-tamoxifen, carboplatin, bortezomib, and X-ray radiation. These data suggest that SET plays important roles in the tumor progression of a subset of canine mammary tumor by suppressing PP2A activity and enhancing mTOR, β-catenin, and NFκB signaling.
format	article
author	Satoru Kake Shunya Tsuji Shuhei Enjoji Sayaka Hanasaki Hiroshi Hayase Ryotaro Yabe Yuiko Tanaka Takayuki Nakagawa Hao-Ping Liu Shih-Chieh Chang Tatsuya Usui Takashi Ohama Koichi Sato
author_facet	Satoru Kake Shunya Tsuji Shuhei Enjoji Sayaka Hanasaki Hiroshi Hayase Ryotaro Yabe Yuiko Tanaka Takayuki Nakagawa Hao-Ping Liu Shih-Chieh Chang Tatsuya Usui Takashi Ohama Koichi Sato
author_sort	Satoru Kake
title	The role of SET/I2PP2A in canine mammary tumors
title_short	The role of SET/I2PP2A in canine mammary tumors
title_full	The role of SET/I2PP2A in canine mammary tumors
title_fullStr	The role of SET/I2PP2A in canine mammary tumors
title_full_unstemmed	The role of SET/I2PP2A in canine mammary tumors
title_sort	role of set/i2pp2a in canine mammary tumors
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9d3996734a2e4ea98d3f019b4c72c5de
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The role of SET/I2PP2A in canine mammary tumors

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