%0 Journal Article
%T Transcription factor Sp1 induces ADAM17 and contributes to tumor cell invasiveness under hypoxia
%A Alexandra Szalad
%A Mark Katakowski
%A Xuguang Zheng
%A Feng Jiang
%A Michael Chopp
%J Journal of Experimental & Clinical Cancer Research
%D 2009
%I BioMed Central
%R 10.1186/1756-9966-28-129
%X 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.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.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.Brain tumors result from abnormal or uncontrolled cell division. Glioma is a highly vascular, very aggressive and extremely invasive primary brain tumor. Hypoxia induces changes in glioma and its microenvironment, which leads to increased aggressiveness and resistance to chemotherapy and radiation [1]. Studies have shown that large areas of hypoxia within glioma correlates inversely with the patient's outcome and survival [1-4].ADAM17 (A Disintegrin and Metalloproteinase-17) also called TACE (TNF-alpha converting enzyme) plays a pivotal role in the processing of numerous growth factor proteins, and has emerged as a new therapeutic target in several tumor types [5-8]. Recent studies showed that when ADAM17 is either inhibited or suppressed there is attenuation in tumor invasiveness and malignancy, resulting in a better outcome for breast cancer patients [9,10].Low levels of oxygen (hypoxia) initiates cellular invasive processes that occur under physiological and pathological conditions such as tumor invasiveness and metastasis [11].Specificity transcription protein-1 (Sp1) is believed to play an important role in the transcription of many genes involved in cancer th
%U http://www.jeccr.com/content/28/1/129