open access

https://hdl.handle.net/2115/53339

Hypoxia-Inducible Factors Activate CD133 Promoter through ETS Family Transcription Factors

英語

2013-06-20

Public library science

Plos one

8(6)

e66255

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.

学術雑誌論文

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Creative Commons Attribution 3.0 Unported

1932-6203