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ID 109497
Title Alternative
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
Author
Kim, Nam-Hee Tokushima University
Chen, Yi-An National Institute of Biomedical Innovation
Matsuo, Taisuke Tokushima University
Komatsu, Masato Tokushima University
Miyoshi, Yasuo Hyogo College of Medicine
Sasa, Mitsunori Tokushima Breast Care Clinic
Mizuguchi, Kenji National Institute of Biomedical Innovation
Keywords
Karyopherin-alpha
estrogen
nuclear translocation
breast cancer
BIG3
PHB2
Content Type
Thesis or Dissertation
Description
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.
Journal Title
PLOS ONE
ISSN
19326203
Publisher
PLOS
Volume
10
Issue
6
Start Page
e0127707
Published Date
2015-06-08
Remark
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。
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2860号
Diploma Number
甲口第399号
Granted Date
2015-07-16
Degree Name
Doctor of Dental Science
Grantor
Tokushima University
departments
Institute of Advanced Medical Sciences
Oral Sciences