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Hypoxia-Inducible Factors Activate CD133 Promoter through ETS Family Transcription Factors
This item is licensed under:Creative Commons Attribution 3.0 Unported
| 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. |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/53339 |
| 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)
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Submitter: 大西 俊介
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