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
リソース情報
ヒト・動物細胞 293(RCB1637)