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ID 109497
タイトル別表記
エストロゲン受容体陽性乳がん細胞において、BIG3は複数のKaryopherin-αを介したPHB2のエストロゲン依存性核移行を阻害する
著者
金, 南希 徳島大学大学院口腔科学教育部(口腔科学専攻)
Chen, Yi-An National Institute of Biomedical Innovation
松尾, 泰佑 Tokushima University
小松, 正人 Tokushima University
Miyoshi, Yasuo Hyogo College of Medicine
Sasa, Mitsunori Tokushima Breast Care Clinic
Mizuguchi, Kenji National Institute of Biomedical Innovation
キーワード
Karyopherin-alpha
estrogen
nuclear translocation
breast cancer
BIG3
PHB2
資料タイプ
学位論文
抄録
We recently reported that brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) binds Prohibitin 2 (PHB2) in cytoplasm, thereby causing a loss of function of the PHB2 tumor suppressor in the nuclei of breast cancer cells. However, little is known regarding the mechanism by which BIG3 inhibits the nuclear translocation of PHB2 into breast cancer cells. Here, we report that BIG3 blocks the estrogen (E2)-dependent nuclear import of PHB2 via the karyopherin alpha (KPNA) family in breast cancer cells. We found that overexpressed PHB2 interacted with KPNA1, KPNA5, and KPNA6, thereby leading to the E2-dependent translocation of PHB2 into the nuclei of breast cancer cells. More importantly, knockdown of each endogenous KPNA by siRNA caused a significant inhibition of E2-dependent translocation of PHB2 in BIG3-depleted breast cancer cells, thereby enhancing activation of estrogen receptor alpha (ERα). These data indicated that BIG3 may block the KPNAs (KPNA1, KPNA5, and KPNA6) binding region(s) of PHB2, thereby leading to inhibition of KPNAs-mediated PHB2 nuclear translocation in the presence of E2 in breast cancer cells. Understanding this regulation of PHB2 nuclear import may provide therapeutic strategies for controlling E2/ERα signals in breast cancer cells.
掲載誌名
PLOS ONE
ISSN
19326203
出版者
PLOS
10
6
開始ページ
e0127707
発行日
2015-06-08
備考
内容要旨・審査要旨・論文本文の公開:
内容要旨 : LID201507301001.pdf
審査要旨 : LID201507301002.pdf
論文本文 : LID201507301003.pdf
本論文は, 著者Nam-Hee Kimの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
Copyright: © 2015 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第2860号
学位記番号
甲口第399号
学位授与年月日
2015-07-16
学位名
博士(歯学)
学位授与機関
徳島大学
部局
先端酵素学研究所
歯学系