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) |