17βE2 promotes cell proliferation in endometriosis by decreasing PTEN via NFκB-dependent pathway

The objective of this study was to explore the mechanism of phosphatase and tensin homolog (PTEN) loss in endometriosis. We found that aberrant PTEN expression and mitogen-activated protein kinases (MAPK)/ERK, phosphoinositide 3-kinase (PI3K)/AKt, and nuclear factor-kappaB (NFκB) signaling overactivities coexisted in endometriosis. In vitro, 17β-estradiol rapidly activated the 3 pathways in endometriotic cells and specific inhibitions on the 3 pathways respectively blocked 17β-estradiol-induced cell proliferation. 17β-estradiol suppressed PTEN transcription and expression in endometriotic cells which was abolished by specific NFκB inhibition.Conclusion(s)Total/nuclear PTEN-loss and MAPK/ERK, PI3K/AKt, and NFκB signal overactivities coexist in endometriosis. In vitro, 17β-estradiol can promotes cell proliferation in endometriosis by activating PI3K/AKt pathway via an NFκB/PTEN-dependent pathway. For the first time we propose the possibility of the presence of a positive feedback-loop: 17β-estradiol → high NFκB → low PTEN → high PI3K → high NFκB, in endometriosis, which may finally promote the proliferation of ectopic endometrial epithelial cells and in turn contributes to the progression of the disease.