論文 - 詳細
| RRC ID | 44517 |
|---|---|
| 著者 | Ohnishi S, Maehara O, Nakagawa K, Kameya A, Otaki K, Fujita H, Higashi R, Takagi K, Asaka M, Sakamoto N, Kobayashi M, Takeda H. |
| タイトル | hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors. |
| ジャーナル | PLoS One |
| 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-1α and HIF-2α). 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-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins. |
| 巻・号 | 8(6) |
| ページ | e66255 |
| 公開日 | 2013-1-1 |
| DOI | 10.1371/journal.pone.0066255 |
| PII | PONE-D-13-05648 |
| PMID | 23840432 |
| PMC | PMC3688781 |
| MeSH | AC133 Antigen Antigens, CD / genetics* Antigens, CD / metabolism Basic Helix-Loop-Helix Transcription Factors / physiology* Binding Sites Cell Hypoxia Cell Line, Tumor Gene Expression Gene Knockdown Techniques Glycoproteins / genetics* Glycoproteins / metabolism HEK293 Cells Humans Hypoxia-Inducible Factor 1, alpha Subunit / physiology* Peptides / genetics* Peptides / metabolism Promoter Regions, Genetic Protein Binding Proto-Oncogene Protein c-ets-1 / physiology* Transcriptional Activation* Up-Regulation ets-Domain Protein Elk-1 / physiology* |
| IF | 2.74 |
| 引用数 | 19 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |