scholarly journals Heparin-Binding Epidermal Growth Factor and Its Receptors Mediate Decidualization and Potentiate Survival of Human Endometrial Stromal Cells

2005 ◽  
Vol 90 (2) ◽  
pp. 913-919 ◽  
Author(s):  
Katya Chobotova ◽  
Natalia Karpovich ◽  
Janet Carver ◽  
Sanjiv Manek ◽  
William J. Gullick ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Stromal Cells ◽  
Heparin Binding ◽  
Endometrial Stromal Cells ◽  
Epidermal Growth

scholarly journals Raf-1, a Potential Therapeutic Target, Mediates Early Steps in Endometriosis Lesion Development by Endometrial Epithelial and Stromal Cells

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3911-3921 ◽  
Author(s):  
Elizabeth M. De La Garza ◽  
Peter A. Binkley ◽  
Manonmani Ganapathy ◽  
Naveen K. Krishnegowda ◽  
Rajeshwar R. Tekmal ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Stromal Cells ◽  
Pelvic Cavity ◽  
Lesion Formation ◽  
Endometrial Stromal Cells ◽  
Peritoneal Mesothelial Cells ◽  
Endometrial Cells ◽  
Retrograde Menstruation ◽  
Epidermal Growth

Endometriosis is a hormone-sensitive gynecological disorder characterized by the benign growth of endometrial-like tissue in the pelvic cavity. Endometriotic lesions composed of endometrial stromal cells (ESC) and glandular epithelial cells (EEC) are thought to arise from menstrual endometrial tissue reaching the pelvic cavity via retrograde menstruation. The cause of endometriotic lesion formation is still not clear. Recent evidence suggest that cytokines may play a role in the early development of endometriosis lesions. Because cytokines and growth factors signal via the v-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) kinase pathway, we have examined the role of Raf-1 in early steps of endometriosis lesion formation, specifically attachment of endometrial cells to peritoneal mesothelial cells (PMC) and invasion of endometrial cells through PMC (trans-mesothelial invasion). Raf-1 antagonist GW5074 decreased attachment to PMC and trans-mesothelial invasion by primary EEC and ESC. Raf-1 also mediated TGFβ-induced trans-mesothelial invasion by the established, low-invasive EEC line EM42. TGFβ treatment of EEC resulted in Raf-1 phosphorylation at S338 and phosphorylation of ERK, suggesting that TGFβ activates Raf-1 signaling in these cells. GW5074 had little effect on ESC proliferation but inhibited EEC growth significantly under reduced serum conditions. Antagonizing Raf-1 activity and expression via GW5074 and specific Raf-1 small interfering RNA, respectively, did not alter EEC resistance to growth inhibition by TGFβ. Raf-1 inhibition blocked induction of EEC growth by epidermal growth factor. Our data suggest that Raf-1 may mediate pathologic steps involved in early endometriosis lesion formation and may be a mediator of TGFβ and epidermal growth factor actions in endometriosis.

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