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Transcription factor Sp1 induces ADAM17 and contributes to tumor cell invasiveness under hypoxia.

Abstract：

BACKGROUND:Expression of the Sp1 transcription factor is induced by hypoxia, and the ADAM17 promoter contains predicted Sp1 binding sites. ADAM17 contributes to hypoxic-induce invasiveness of glioma. In this study, we investigated whether Sp1 transcription factor induces ADAM17 and/or contributes to tumor cell invasiveness in hypoxia. METHODS:Employing RT-PCR and Western blot, we examined the role of Sp1 in ADAM17 transcription/expression under normoxic and hypoxic conditions, and whether it binds to the ADAM17 GC-rich promoter region using a chromatin immunoprecipitation assay. Additionally, we tested the effect of Sp1 suppression in tumor cell invasion and migration, using Matrigel basement membrane invasion chambers, a scratch wound-healing assay, and small interfering RNA. RESULTS:Here, we found that Sp1 binds to the ADAM17 promoter, and that Sp1 regulates ADAM17 expression under hypoxia. Furthermore, suppression of Sp1 decreases invasiveness and migration in U87 tumor cells. CONCLUSION:Our findings suggest the Sp1 transcription factor mediates ADAM17 expression under hypoxia, regulates glioma invasiveness, and thus, may be a target for anti-invasion therapies.

journal_name

J Exp Clin Cancer Res

journal_title

Journal of experimental & clinical cancer research : CR

authors

Szalad A,Katakowski M,Zheng X,Jiang F,Chopp M

doi

10.1186/1756-9966-28-129

subject

Has Abstract

pub_date

2009-09-22 00:00:00

pages

129

eissn

0392-9078

issn

1756-9966

pii

1756-9966-28-129

journal_volume

28

pub_type

杂志文章

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