Mol. Hum. Reprod. Advance Access originally published online on March 25, 2004
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Molecular Human Reproduction, Vol. 10, No. 6, pp. 399-407, 2004
© European Society of Human Reproduction and Embryology 2004
Cyr61, a deregulated gene in endometriosis
1Institute of Anatomy, University Hospital, 45122 Essen, 2Research Laboratories of Schering AG, 13342 Berlin, 3Department of Orthopaedy, University of Wuerzburg, 97074 Wuerzburg and 4Department of Gynaecology, University Hospital, 49076 Osnabrueck, Germany 6Both authors contributed equally to this study.
5 To whom correspondence should be addressed. e-mail: e.winterhager{at}uni-essen.de
Gene expression profiling was performed to identify genes involved in the development of endometriosis. In the secretory phase of the menstrual cycle, several estrogen-regulated genes were up-regulated in endometria of women with endometriosis. The most consistent regulation with one of the highest factors was observed for the Cyr61 gene, which codes for a secreted, cysteine-rich, heparin-binding protein that promotes cell adhesion, migration, and neovascularization. Estrogen responsiveness of endometrial Cyr61 expression was suggested by the higher expression during the proliferative phase and the reduction observed in human endometrial fragments grafted into nude mice subsequently treated with an anti-estrogen. The expression level of Cyr61 was found to be further increased in ectopic endometriotic lesions, as compared to eutopic endometria. In these lesions, an imbalance in expression of the estrogen-converting enzymes 17ß-hydroxysteroid dehydrogenase type 1 and 2 was found, which might explain the elevated Cyr61 level. However, Cyr61 expression was not altered in endometriotic lesions of women treated with a GnRH agonist. These results suggest that Cyr61 may represent a gene characteristic for endometriosis and also play an important role in the development and persistence of endometriotic lesions.
Key words: Cyr61/endometriosis/estrogen/human endometrium/microarray
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