Hypoxia upregulates expression of human endosialin gene via hypoxia-inducible factor 2.

Abstract:

:Endosialin is a transmembrane glycoprotein selectively expressed in blood vessels and stromal fibroblasts of various human tumours. It has been functionally implicated in angiogenesis, but the factors that control its expression have remained unclear. As insufficient delivery of oxygen is a driving force of angiogenesis in growing tumours, we investigated whether hypoxia regulates endosialin expression. Here, we demonstrate that endosialin gene transcription is induced by hypoxia predominantly through a mechanism involving hypoxia-inducible factor-2 (HIF-2) cooperating with the Ets-1 transcription factor. We show that HIF-2 activates the endosialin promoter both directly, through binding to a hypoxia-response element adjacent to an Ets-binding site in the distal part of the upstream regulatory region, and indirectly, through Ets-1 and its two cognate elements in the proximal promoter. Our data also suggest that the SP1 transcription factor mediates responsiveness of the endosialin promoter to high cell density. These findings elucidate important aspects of endosialin gene regulation and provide a rational frame for future investigations towards better understanding of its biological significance.

journal_name

Br J Cancer

authors

Ohradanova A,Gradin K,Barathova M,Zatovicova M,Holotnakova T,Kopacek J,Parkkila S,Poellinger L,Pastorekova S,Pastorek J

doi

10.1038/sj.bjc.6604685

subject

Has Abstract

pub_date

2008-10-21 00:00:00

pages

1348-56

issue

8

eissn

0007-0920

issn

1532-1827

pii

6604685

journal_volume

99

pub_type

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