CYR61 regulation in human endometrium

Isabella Gashaw, Yvonne Absenger, Elke Winterhager
In: Experimental and Clinical Endocrinology & Diabetes · 2004 · vol. 112(S 1) · doi:10.1055/s-2004-819128 · W2328115418
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study investigated CYR61 gene activation in human endometrial cells, finding that growth factors like EGF and bFGF significantly increased its mRNA expression, while PMA induced it in specific cell lines.

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This paper investigated the regulatory mechanisms and signaling pathways controlling expression of CYR61/CCN1, an angiogenic immediate-early gene, in human endometrium. Using tumor-derived endometrial cell lines Ishikawa and RL-95, the authors found that CYR61 is expressed and secreted, with only moderate regulation by estrogen and other steroids regardless of estrogen receptor status, while EGF, bFGF, and other growth factors significantly increased CYR61 mRNA after about 30 minutes and PMA induced CYR61 in RL-95 with maximal effect at 2 hours. They compared induction of CYR61 with expression of different MAP kinases to provide initial insight into involved signaling pathways, but the study relied on cell lines rather than primary endometrial tissue. This paper is centrally about endometriosis — it builds on prior findings that CYR61 is upregulated in endometriosis-associated endometria and in endometriotic lesions, and it examines how CYR61 regulation by estrogen and growth-factor signaling may relate to lesion development and persistence.

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Abstract

Cysteine-rich protein 61 (CYR61/CCN1) is an angiogenic factor and a member of a family of growth factor-inducible immediate-early genes with functions in cell adhesion, proliferation and differentiation. Previously, we have shown that CYR61 is upregulated in endometria of women with endometriosis and is highly expressed in endometriotic lesions. CYR61 is regulated by estrogen suggesting an important role in the development and persistence of endometriotic lesions. Therfore, we investigated the regulatory mechanisms and signaling pathways involved in CYR61 gene activation in human endometrium. Tumor derived human endometrial cell lines Ishikawa and RL-95 express and secrete the CYR61 protein. However, we found only a moderate regluation by estrogen and other steroides, independent on the estrogen receptor status. Incubations with EGF, bFGF and other growth factors increased the expression levels of CYR61 mRNA significantly after 30 minutes. The mitogenic phorbol myristate acetate (PMA) showed inductive properties for CYR61 in RL-95 cells with a maximal effect after 2h of incubation. The expression levels of different MAP-kinases were compared with the induction of CYR61. The results give a first insight into regulation of CYR61 in human endometrium.
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Subscribe to RSS DOI: 10.1055/s-2004-819128 CYR61 regulation in human endometrium Cysteine-rich protein 61 (CYR61/CCN1) is an angiogenic factor and a member of a family of growth factor-inducible immediate-early genes with functions in cell adhesion, proliferation and differentiation. Previously, we have shown that CYR61 is upregulated in endometria of women with endometriosis and is highly expressed in endometriotic lesions. CYR61 is regulated by estrogen suggesting an important role in the development and persistence of endometriotic lesions. Therfore, we investigated the regulatory mechanisms and signaling pathways involved in CYR61 gene activation in human endometrium. Tumor derived human endometrial cell lines Ishikawa and RL-95 express and secrete the CYR61 protein. However, we found only a moderate regluation by estrogen and other steroides, independent on the estrogen receptor status. Incubations with EGF, bFGF and other growth factors increased the expression levels of CYR61 mRNA significantly after 30 minutes. The mitogenic phorbol myristate acetate (PMA) showed inductive properties for CYR61 in RL-95 cells with a maximal effect after 2h of incubation. The expression levels of different MAP-kinases were compared with the induction of CYR61. The results give a first insight into regulation of CYR61 in human endometrium.

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