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  1. 原著論文

High-incidence spontaneous tumors in JF1/Ms mice: relevance of hypomorphic germline mutation and subsequent promoter methylation of Ednrb

https://repo.qst.go.jp/records/47004
https://repo.qst.go.jp/records/47004
38e30d03-0a89-4ac5-8724-b882403928e8
Item type 学術雑誌論文 / Journal Article(1)
公開日 2014-12-19
タイトル
タイトル High-incidence spontaneous tumors in JF1/Ms mice: relevance of hypomorphic germline mutation and subsequent promoter methylation of Ednrb
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 Watanabe, Junko

× Watanabe, Junko

WEKO 469200

Watanabe, Junko

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Kaneko, Yasuhiko

× Kaneko, Yasuhiko

WEKO 469201

Kaneko, Yasuhiko

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Kurosumi, Masafumi

× Kurosumi, Masafumi

WEKO 469202

Kurosumi, Masafumi

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Kobayashi, Yasuhito

× Kobayashi, Yasuhito

WEKO 469203

Kobayashi, Yasuhito

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Sakamoto, Michihiro

× Sakamoto, Michihiro

WEKO 469204

Sakamoto, Michihiro

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A., Yoshida Mitsuaki

× A., Yoshida Mitsuaki

WEKO 469205

A., Yoshida Mitsuaki

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穐山, 美穂

× 穐山, 美穂

WEKO 469206

穐山, 美穂

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Matsushima, Yoshibumi

× Matsushima, Yoshibumi

WEKO 469207

Matsushima, Yoshibumi

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穐山 美穂

× 穐山 美穂

WEKO 469208

en 穐山 美穂

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抄録
内容記述タイプ Abstract
内容記述 PURPOSE:
\nJF1/Ms mice, an inbred strain derived from Japanese wild mice, carry a germline hypomorphic mutation in the endothelin receptor type B gene (Ednrb). We observed that the JF1/Ms mice develop various spontaneous tumors at a high incidence late in life. The aim of this study was to elucidate the mechanism responsible for spontaneous tumors in these mice. Possible relevance of milk-borne mammary tumor virus and gene alterations in Ednrb to tumorigenesis was explored.
\nMETHODS:
\nExpression and methylation status of Ednrb were quantitatively analyzed in normal and cancer tissues of mammary gland, liver, submandibular gland as well as in a cultured cell line, MW1, established from a submandibular gland adenocarcinoma. The biological effects of EDNRB were examined in the MW1 cells transfected with wild-type Ednrb.
\nRESULTS:
\nTranscripts of Ednrb were barely detectable, and the promoter region of Ednrb was hypermethylated in tumor tissues and the MW1 cells. In contrast, normal counterpart tissues showed positive expression of Ednrb transcripts and had unmethylated promoter regions. Treatment of the MW1 cells with 5-Aza-dC restored transcription of Ednrb to normal levels. Transfection of the MW1 cells with Ednrb1 (MW1-Ednrb1) resulted in lower growth rates and morphological changes compared with the mock-transfected MW1 cells (MW1-mock1). Furthermore, the MW1-Ednrb1 cells transplanted in syngeneic mice showed a lower proliferation rate than the MW1-mock1 cells.
\nCONCLUSIONS:
\nGermline mutation and subsequent promoter methylation of Ednrb may be relevant to cancer susceptibility in the JF1/Ms mice. These data indicate that Ednrb acts as a tumor suppressor, as reported in human prostate, bladder, and clear cell renal carcinomas.
書誌情報 Journal of Cancer Research and Clinical Oncology

巻 140, 号 1, p. 99-107, 発行日 2014-01
出版者
出版者 Springer
ISSN
収録物識別子タイプ ISSN
収録物識別子 0171-5216
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