Hypoxia-Inducible Factors Activate CD133 Promoter through ETS Family Transcription Factors
抄録
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.
収録刊行物
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- Plos one
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Plos one 8 (6), e66255-, 2013-06-20
Public library science
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詳細情報 詳細情報について
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- CRID
- 1050001339014468352
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- NII論文ID
- 120005326763
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- HANDLE
- 2115/53339
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- ISSN
- 19326203
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- CiNii Articles