ヒグチ　ケイ   Higuchi Kei   樋口　慧    所属   東邦大学  薬学部 薬学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Estrogen receptor α induction by mitoxantrone increases Abcg2 expression in placental trophoblast cells.
掲載誌名	正式名：Journal of pharmaceutical sciences ISSNコード：0022-3549/1520-6017
掲載区分	国外
出版社	WILEY-BLACKWELL
巻・号・頁	102(9),pp.3364-72
著者・共著者	Kenji Oda,Tomohiro Nishimura,Kei Higuchi,Naomi Ishido,Kaori Ochi,Hisashi Iizasa,Yoshimichi Sai,Masatoshi Tomi,Emi Nakashima
発行年月	2013/09
概要	Substrate-induced upregulation of ATP-binding cassette subfamily G member 2 (ABCG2) has been well studied in cancer cells, but it is also important to understand whether ABCG2 is upregulated by its substrates in tissues in which it is constitutively expressed. In the present study, we aimed to clarify the regulatory mechanism of Abcg2 expression by its substrate, mitoxantrone, in placental cells. Abcg2 mRNA expression in rat placental TR-TBT 18d-1 cells treated with 10 μM mitoxantrone for 24 h was increased, compared with that in nontreated cells, whereas 10 μM pheophorbide-a had no effect. Methylated CpG level in the promoter region of the Abcg2 gene was low and was not altered by mitoxantrone. On the contrary, mitoxantrone markedly increased the expression of estrogen receptor (ER) α and progesterone receptor (PR) B. Fulvestrant, an ER antagonist, attenuated the mitoxantrone-induced increase of Abcg2 mRNA expression, whereas mifepristone, a PR antagonist, had little effect. 17β-estradiol, an ER ligand, positively regulated the mitoxantrone-induced increase of Abcg2 expression. DNA demethylation by 5-aza-2-deoxycytidine treatment increased ERα expression, but mitoxantrone failed to facilitate the demethylation of ERα promoter in TR-TBT 18d-1 cells. In conclusion, Abcg2 expression is induced by mitoxantrone via the induction of ERα in TR-TBT 18d-1 cells.
DOI	10.1002/jps.23549
PMID	23592396