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Cited by 104Cancer, Hypoxia, and MetabolismAngiogenesis and VEGF in CancerConnective Tissue Growth Factor Research

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Mechanisms of Hypoxic Gene Regulation of Angiogenesis Factor Cyr61 in Melanoma Cells

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Kunz, Manfred, Moeller, Steffen, Koczan, Dirk, Lorenz, Peter, Wenger, Roland H., Glocker, Michael O., Thiesen, Hans-Juergen, Gross, Gerd, Ibrahim, Saleh M.·2003·Journal of Biological Chemistry
DOI 10.1074/jbc.m301373200
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Abstract

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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Research works printed but not linked: 11

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Metadata

Authors
Kunz, M., Moeller, S., Koczan, D., Lorenz, P., Wenger, R. H., Glocker, M. O., Thiesen, H.-J., Gross, G., & Ibrahim, S. M.
Affiliations
  • University of Rostock (DE)
  • Leipzig University (DE)
Corresponding author
Kunz, Manfred
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-11
Volume
278
Issue
46
Pages
45651-45660
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m301373200
OpenAlex
W1988530720
Cited by
104
References
67
Citations by year
2026: 2 · 2025: 1 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 4
FWCI
3.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
  • Zurich Open Repository and Archive (University of Zurich)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
Keywords
CYR61, hypoxia, melanoma, angiogenesis, hypoxia-responsive genes, hypoxia-inducible factor-1α, AP-1, c-Jun, transcriptional regulation, tumor progression, tumor aggressiveness, tumor stage
MeSH terms
Hypoxia, Humans, Luciferases, Melanoma, Plasmids, Promoter Regions, Genetic, Protein Binding, RNA, Time Factors, Transcription Factors, Blotting, Northern, Gene Expression Regulation, Neoplastic, Mutagenesis, Protein Structure, Tertiary, Immediate-Early Proteins, DNA, Complementary, Jurkat Cells, Oligonucleotide Array Sequence Analysis, Amino Acid Motifs, Intercellular Signaling Peptides and Proteins, Cell Line, Tumor, Hypoxia-Inducible Factor 1, alpha Subunit, Cysteine-Rich Protein 61

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