|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print August 25, 2003
Department of Dermatology and Venereology, University of Rostock, Rostock 18055
Corresponding Author: manfred.kunz{at}med.uni-rostock.de
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 Affymetrixâ gene chip system was used to analyse five melanoma cell lines of different aggressiveness. Hundred and sixty 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, 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, EMSA and immunoprecipitation that hypoxia-inducible factor (HIF)-1a, 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 towards melanoma cells with constitutive high Cyr61 expression.
J. Biol. Chem, 10.1074/jbc.M301373200
Submitted on February 7, 2003
Revised on August 25, 2003
Accepted on August 25, 2003
Mechanisms of hypoxic gene regulation of angiogenesis factor Cyr61 in melanoma cells
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Monnier, P. Farmer, G. Bieler, N. Imaizumi, T. Sengstag, G. C. Alghisi, J.-C. Stehle, L. Ciarloni, S. Andrejevic-Blant, R. Moeckli, et al. CYR61 and {alpha}V{beta}5 Integrin Cooperate to Promote Invasion and Metastasis of Tumors Growing in Preirradiated Stroma Cancer Res., September 15, 2008; 68(18): 7323 - 7331. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Meyuhas, E. Pikarsky, E. Tavor, A. Klar, R. Abramovitch, J. Hochman, T. G. Lago, and A. Honigman A Key Role for Cyclic AMP-Responsive Element Binding Protein in Hypoxia-Mediated Activation of the Angiogenesis Factor CCN1 (CYR61) in Tumor Cells Mol. Cancer Res., September 1, 2008; 6(9): 1397 - 1409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Gashaw, S. Stiller, C. Boing, R. Kimmig, and E. Winterhager Premenstrual Regulation of the Pro-Angiogenic Factor CYR61 in Human Endometrium Endocrinology, May 1, 2008; 149(5): 2261 - 2269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Aydin, S. Signorelli, T. Lechleitner, M. Joannidis, C. Pleban, P. Perco, W. Pfaller, and P. Jennings Influence of microvascular endothelial cells on transcriptional regulation of proximal tubular epithelial cells Am J Physiol Cell Physiol, February 1, 2008; 294(2): C543 - C554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Quan, T. He, Y. Shao, L. Lin, S. Kang, J. J. Voorhees, and G. J. Fisher Elevated Cysteine-Rich 61 Mediates Aberrant Collagen Homeostasis in Chronologically Aged and Photoaged Human Skin Am. J. Pathol., August 1, 2006; 169(2): 482 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Gashaw, J. M. Hastings, K. S. Jackson, E. Winterhager, and A. T. Fazleabas Induced Endometriosis in the Baboon (Papio anubis) Increases the Expression of the Proangiogenic Factor CYR61 (CCN1) in Eutopic and Ectopic Endometria Biol Reprod, June 1, 2006; 74(6): 1060 - 1066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. van Waveren, Y. Sun, H. S. Cheung, and C. T. Moraes Oxidative phosphorylation dysfunction modulates expression of extracellular matrix--remodeling genes and invasion Carcinogenesis, March 1, 2006; 27(3): 409 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. R. Pendurthi, T. T. Tran, M. Post, and L. V. M. Rao Proteolysis of CCN1 by Plasmin: Functional Implications Cancer Res., November 1, 2005; 65(21): 9705 - 9711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Manalo, A. Rowan, T. Lavoie, L. Natarajan, B. D. Kelly, S. Q. Ye, J. G. N. Garcia, and G. L. Semenza Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1 Blood, January 15, 2005; 105(2): 659 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Abramovitch, E. Tavor, J. Jacob-Hirsch, E. Zeira, N. Amariglio, O. Pappo, G. Rechavi, E. Galun, and A. Honigman A Pivotal Role of Cyclic AMP-Responsive Element Binding Protein in Tumor Progression Cancer Res., February 15, 2004; 64(4): 1338 - 1346. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |