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.