イチノエ　アキマサ   AKIMASA ICHINOE   一戸　晶元    所属   医学部 医学科（附属足立医療センター）    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Regulation Mechanism of TWIST1 Transcription by BHLHE40 and BHLHE41 in Cancer Cells.
掲載誌名	正式名：Molecular and cellular biology 略　 称：Mol Cell Biol ISSNコード：02707306/10985549
掲載区分	国外
巻・号・頁	35(24),pp.4096-4109
総ページ数	14
著者・共著者	Kazuo Asanoma†, Ge Liu, Takako Yamane, Yoko Miyanari, Tomoka Takao, Hiroshi Yagi, Tatsuhiro Ohgami, Akimasa Ichinoe, Kenzo Sonoda, Norio Wake, Kiyoko Kato
発行年月	2015/12
概要	BHLHE40 and BHLHE41 (BHLHE40/41) are basic helix-loop-helix type transcription factors that play key roles in multiple cell behaviors. BHLHE40/41 were recently shown to be involved in an epithelial-to-mesenchymal transition (EMT). However, the precise mechanism of EMT control by BHLHE40/41 remains unclear. In the present study, we demonstrated that BHLHE40/41 expression was controlled in a pathological stage-dependent manner in human endometrial cancer (HEC). Our in vitro assays showed that BHLHE40/41 suppressed tumor cell invasion. BHLHE40/41 also suppressed the transcription of the EMT effectors SNAI1, SNAI2, and TWIST1. We identified the critical promoter regions of TWIST1 for its basal transcriptional activity. We elucidated that the transcription factor SP1 was involved in the basal transcriptional activity of TWIST1 and that BHLHE40/41 competed with SP1 for DNA binding to regulate gene transcription. This study is the first to report the detailed functions of BHLHE40 and BHLHE41 in the suppression of EMT effectors in vitro. Our results suggest that BHLHE40/41 suppress tumor cell invasion by inhibiting EMT in tumor cells. We propose that BHLHE40/41 are promising markers to predict the aggressiveness of each HEC case and that molecular targeting strategies involving BHLHE40/41 and SP1 may effectively regulate HEC progression.
DOI	10.1128/MCB.00678-15