Endometriotic stromal cells lose the ability to regulate cell-survival signaling in endometrial epithelial cells in vitro.
In normal endometrium, stromal factors regulate the growth of epithelial cells. However, epithelial cells in endometriotic lesions display increased proliferation and decreased apoptosis. This work tested the hypothesis that in endometriosis stromal cells lose the ability to regulate survival signaling and cell growth in epithelial cells. Primary normal, endometriotic eutopic and ectopic epithelial cells were cultured in the presence of medium conditioned by normal, eutopic and ectopic endometriotic endometrial stromal cells. Endometriotic epithelial cells showed higher Survivin expression than normal epithelial cells. Conditioned medium (CM) from normal or eutopic endometriotic stromal cells significantly inhibited the Survivin expression and AKt phosphorylation in normal or eutopic endometriotic epithelial cells. However, CM from ectopic endometriotic stromal cells did not have an inhibitory effect on normal or ectopic endometriotic epithelial cells. Inhibition of AKt phosphorylation and Survivin expression in normal or eutopic endometriotic epithelial cells in the presence of stromal factors from normal or eutopic endometriotic stromal cells was enhanced by progesterone, whereas progesterone had little effect in the presence of stromal factors from ectopic endometriotic stromal cells. The inability of ectopic endometriotic stromal cells to regulated PI3K/AKt/Survivin signaling and mediate the progesterone response in endometriotic epithelial cells may facilitate epithelial cell proliferation in endometriosis and promote the survival of endometriotic lesions.
Zhang
Hui
H
Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, People's Republic of China.
Li
Mingjiang
M
Zheng
Xiaojing
X
Sun
Ying
Y
Wen
Zeqing
Z
Zhao
Xingbo
X
D000328:Adult; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology*; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D000077022:Survivin
C107489:BIRC5 protein, human; D002867:Chromones; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D000077022:Survivin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one