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.

• Authors: Alexandra Szalad, Mark Katakowski, Xuguang Zheng, Feng Jiang, Michael Chopp
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 28 Pg. 129 (Sep 22 2009) ISSN: 1756-9966 [Electronic] England
• PMID: 19772640 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Immunoglobulins
• SP1 antigen
• ADAM Proteins
• ADAM17 Protein
• ADAM17 protein, human

Topics

• ADAM Proteins (genetics, metabolism)
• ADAM17 Protein
• Blotting, Western
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Hypoxia (physiology)
• Cell Movement (genetics)
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, metabolism, pathology)
• Humans
• Immunoglobulins (genetics, metabolism)
• Immunoprecipitation
• Neoplasm Invasiveness (genetics)
• Promoter Regions, Genetic
• Reverse Transcriptase Polymerase Chain Reaction