| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2017-10-03 |
| タイトル |
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タイトル |
Decreased responsiveness of naturally occurring mutants of human estrogen receptor α to estrogens and antiestrogens |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| ID登録 |
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ID登録 |
10.24517/00013100 |
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ID登録タイプ |
JaLC |
| 著者 |
Komagata, Sayaka
Nakajima, Miki
Tsuchiya, Yuki
Kato, Miki
Kizu, Ryoichi
Kyo, Satoru
Yokoi, Tsuyoshi
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| 著者別表示 |
中嶋, 美紀
木津, 良一
京, 哲
横井, 毅
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| 提供者所属 |
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内容記述タイプ |
Other |
|
内容記述 |
金沢大学ナノ生命科学研究所 / 金沢大学大学院医学系研究科機能分子医薬学 |
| 書誌情報 |
Journal of Steroid Biochemistry and Molecular Biology
巻 100,
号 1-3,
p. 79-86,
発行日 2006-07-01
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| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0960-0760 |
| DOI |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1016/j.jsbmb.2006.02.006 |
| 出版者 |
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出版者 |
Elsevier |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Estrogen receptor α (ERα) is a ligand-inducible transcription factor that mediates the biological effects of estrogens and antiestrogens. Many point mutations in the human ERα gene have been reported to be associated with breast cancer, endometrial cancer, and psychiatric diseases. However, functional analyses for most mutants with amino acid changes are still lacking. In the present study, to investigate the effects of point mutations on the function, gel-shift assays and luciferase assays were performed for eight kinds of mutated ERα proteins, including a single nucleotide change of C207G (N69K), G478T (G160C), T887C (L296P), A908G (K303R), C926T (S309F), A1058T (E353V), A1186G (M396V), and G1231deletion (411fsX7). The mutated ERα expression plasmids were constructed by site-directed mutagenesis. With gel-shift assays using in vitro translated ERα proteins, binding to the consensus estrogen response element (ERE) was observed for the mutated ERα proteins except ERα (G160C) and ERα (411fsX7), the binding of which was comparable with that of the wild type. Western blot analyses showed that ERα (G160C) could not be efficiently translated with the in vitro transcription/translation system and that ERα (411fsX7) produced a truncated protein. To investigate the transactivation potency, wild-type or mutated ERα expression plasmids were co-transfected with pGL3-3EREc38 reporter plasmid into human breast adenocarcinoma MDA-MB-435 cells. The concentration-response curves (10 pM-100 nM E2) of the mutant ERα proteins except ERα (E353V) and ERα (411fsX7) were similar to that of wild-type ERα. However, at a low level of E2 (100 pM), the mutants ERα (N69K), ERα (L296P), ERα (S309F), and ERα (M396V) showed a significant decrease of transactivation compared with that of the wild-type ERα. The mutants ERα (E353V) and ERα (411fsX7) did not show responsiveness to E2 and antiestrogens, 4-hydroxytamoxifen (4OHT) and ICI 182,780. The mutant ERα (S309F) showed decreased responsiveness for the antiestrogenicity of 4OHT. In conclusion, we found that some of the naturally occurring human ERα mutants with amino acid changes may have an altered responsiveness to estrogen and antiestrogens. © 2006 Elsevier Ltd. All rights reserved. |
| 著者版フラグ |
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出版タイプ |
AM |
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出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 関連URI |
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識別子タイプ |
URI |
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関連識別子 |
http://www.elsevier.com/locate/issn/09600760 |
ME-PR-NAKAJIMA-M-02.pdf (96.6 kB)
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