Inhibition of epidermal growth factor receptor restores decidualization markers in stromal fibroblasts from women with endometriosis

David W. Erikson, Joseph C. Chen, Terhi T. Piltonen, Terhi T. Piltonen, Marco Conti, Juan C. Irwin, Linda C. Giudice

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Purpose: Decidualization comprises specific biochemical and morphological changes in uterine endometrium essential for establishment of pregnancy. This process is abnormal in women with endometriosis, a disorder in which endometrial-like tissue is present outside the uterus. The aim of this study was to restore cAMP-induced decidualization marker expression in endometrial stromal fibroblasts from women with endometriosis by using chemical inhibitors to PI3K/AKT/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK) and epidermal growth factor receptor (EGFR) signaling pathways in vitro.

Methods: Endometrial stromal fibroblasts (eSF) from women with (eSFendo) and without (eSFnon-endo) endometriosis were treated with inhibitors to EGFR tyrosine kinase (gefitinib), mTOR (rapamycin) and MAPK kinase 1/2 (MEK1/2) (UO126) during 8-bromoadenosine 3’,5’-cyclic monophosphate (8-br-cAMP)–stimulated decidualization. Decidualization was assessed by evaluating expression of insulin growth factor binding protein 1 (IGFBP1), prolactin (PRL) and forkhead box protein O1A (FOXO1A) by quantitative real-time PCR.

Results: Gefitinib restored expression of decidualization markers in eSFendo to levels consistent with those in eSFnon-endo. Elevated levels of phosphorylated mTOR in eSFendo were reduced to levels found in eSFnon-endo, by gefitinib during treatment with 8-br-cAMP. Additional gene expression analyses suggested dysregulation of EGFR negative feedback regulators in eSFendo.

Conclusions: Results implicate EGFR signaling as an underlying cause for aberrant cAMP-induced decidualization in women with endometriosis, and provide a potential target for management of infertility associated with the disease. The reduction of p-mTOR levels in eSFendo during 8-br-cAMP treatment suggests cooperation between EGR and protein kinase A signaling in the regulation of mTOR in eSF.

Original languageEnglish (US)
Pages (from-to)196-211
Number of pages16
JournalJournal of Endometriosis and Pelvic Pain Disorders
Issue number4
StatePublished - Oct 1 2014
Externally publishedYes


  • Decidualization
  • Endometriosis
  • Epidermal growth factor receptor
  • Fibroblast
  • Mammalian target of rapamycin
  • Mitogen-activated protein kinase

ASJC Scopus subject areas

  • Obstetrics and Gynecology


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