Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-1286
Kunz, M; Moeller, S; Koczan, D; Lorenz, P; Wenger, R H; Glocker, M O; Thiesen, H J; Gross, G; Ibrahim, S M (2003). Mechanisms of hypoxic gene regulation of angiogenesis factor Cyr61 in melanoma cells. Journal of Biological Chemistry, 278(46):45651-45660.
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Hypoxia has a profound influence on progression and metastasis of malignant tumors. In the present report, we used the oligonucleotide microarray technique to identify new hypoxia-inducible genes in malignant melanoma with a special emphasis on angiogenesis factors. A commercially available Affymetrix gene chip system was used to analyze five melanoma cell lines of different aggressiveness. A total of 160 hypoxia-inducible genes were identified, clustering in four different functional clusters. In search of putative angiogenesis and tumor progression factors within these clusters, Cyr61, a recently discovered angiogenesis factor, was identified. Cyr61 was hypoxia-inducible in low aggressive melanoma cells; however, it showed constitutive high expression in highly aggressive melanoma cells. Further analyses of transcriptional mechanisms underlying Cyr61 gene expression under hypoxia demonstrated that an AP-1 binding motif within the Cyr61 promoter plays a central role in the hypoxic regulation of Cyr61. It could be shown by use of in vitro luciferase assays, electrophoretic mobility shift assays, and immunoprecipitation that hypoxia-inducible factor-1alpha interacts with c-Jun/AP-1 and may thereby contribute to Cyr61 transcriptional regulation under hypoxia. Taken together, the presented data show that Cyr61 is a hypoxia-inducible angiogenesis factor in malignant melanoma with tumor stage-dependent expression. This may argue for a hypoxia-induced selection process during tumor progression toward melanoma cells with constitutive high Cyr61 expression.
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|Item Type:||Journal Article, refereed|
|Communities & Collections:||04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
|DDC:||570 Life sciences; biology|
|Deposited On:||11 Feb 2008 12:22|
|Last Modified:||27 Nov 2013 20:52|
|Publisher:||American Society for Biochemistry and Molecular Biology|
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