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Hypoxia-Inducible Factors Activate CD133 Promoter through ETS Family Transcription Factors

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Title: Hypoxia-Inducible Factors Activate CD133 Promoter through ETS Family Transcription Factors
Authors: Ohnishi, Shunsuke Browse this author →KAKEN DB
Maehara, Osamu Browse this author
Nakagawa, Koji Browse this author →KAKEN DB
Kameya, Ayano Browse this author
Otaki, Kanako Browse this author
Fujita, Hirotoshi Browse this author
Higashi, Ryosuke Browse this author
Takagi, Kikuko Browse this author
Asaka, Masahiro Browse this author →KAKEN DB
Sakamoto, Naoya Browse this author →KAKEN DB
Kobayashi, Masanobu Browse this author
Takeda, Hiroshi Browse this author →KAKEN DB
Issue Date: 20-Jun-2013
Publisher: Public library science
Journal Title: Plos one
Volume: 8
Issue: 6
Start Page: e66255
Publisher DOI: 10.1371/journal.pone.0066255
PMID: 23840432
Abstract: CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1-P5) of CD133 in human embryonic kidney (HEK) 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1 alpha and HIF-2 alpha). Deletion and mutation analysis identified one of the two E-twenty six (ETS) binding sites (EBSs) in the P5 region as being essential for its promoter activity induced by HIF-1 alpha and HIF-2 alpha. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1 alpha and HIF-2 alpha bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1 alpha physically interacts with Elk1; however, HIF-2 alpha did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1 alpha and HIF-2 alpha resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1 alpha and HIF-2 alpha activate CD133 promoter through ETS proteins.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 大西 俊介

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