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17betaE2 promotes cell proliferation in endometriosis by decreasing PTEN via NFkappaB-dependent pathway

Hui Zhang1, Xingbo Zhao, Shu Liu

  • 1Department of Obstetrics & Gynecology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, PR China.

Molecular and Cellular Endocrinology
|November 26, 2009
PubMed
Abstract

Insights

Endometriosis involves phosphatase and tensin homolog (PTEN) loss and overactive signaling pathways. 17beta-estradiol promotes cell proliferation via a nuclear factor-kappaB (NFkappaB)/PTEN pathway, potentially creating a disease-driving feedback loop.

Area of Science:

  • Reproductive biology
  • Molecular endocrinology
  • Cell signaling

Background:

  • Endometriosis is characterized by aberrant phosphatase and tensin homolog (PTEN) expression.
  • Overactivity in mitogen-activated protein kinases (MAPK)/ERK, phosphoinositide 3-kinase (PI3K)/AKt, and nuclear factor-kappaB (NFkappaB) signaling pathways is observed in endometriosis.

Purpose of the Study:

  • To elucidate the mechanism underlying PTEN loss in endometriosis.
  • To investigate the role of 17beta-estradiol in regulating PTEN expression and associated signaling pathways in endometriotic cells.

Main Methods:

  • In vitro studies using endometriotic cells.
  • Assessment of PTEN expression and activation of MAPK/ERK, PI3K/AKt, and NFkappaB signaling pathways.
  • Utilized specific pathway inhibitors to block 17beta-estradiol-induced effects.

Main Results:

  • 17beta-estradiol rapidly activated MAPK/ERK, PI3K/AKt, and NFkappaB pathways in endometriotic cells.
  • Inhibition of these pathways blocked 17beta-estradiol-induced cell proliferation.
  • 17beta-estradiol suppressed PTEN transcription and expression, an effect abolished by NFkappaB inhibition.

Conclusions:

  • Total/nuclear PTEN loss and overactive MAPK/ERK, PI3K/AKt, and NFkappaB signaling coexist in endometriosis.
  • 17beta-estradiol promotes endometriotic cell proliferation via PI3K/AKt activation through an NFkappaB/PTEN-dependent pathway.
  • A potential positive feedback loop involving 17beta-estradiol, NFkappaB, PTEN, and PI3K may drive ectopic endometrial cell proliferation and disease progression.

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