Unremitting cell proliferation in the secretory phase of eutopic endometriosis: involvement of pAkt and pGSK3β

Reprod Sci. 2015 Apr;22(4):502-10. doi: 10.1177/1933719114549843. Epub 2014 Sep 6.

Abstract

Objective: Endometriosis is linked to altered cell proliferation and stem cell markers c-kit/stem cell factor (SCF) in ectopic endometrium. Our aim was to investigate whether c-kit/SCF also plays a role in eutopic endometrium.

Design: Eutopic endometrium obtained from 35 women with endometriosis and 25 fertile eumenorrheic women was analyzed for in situ expression of SCF/c-kit, Ki67, RAC-alpha serine/threonine-protein kinase (Akt), phosphorylated RAC-alpha serine/threonin-protein kinase (pAkt), Glycogen synthase kinase 3 beta (GSK3β), and phosphorylated glycogen synthase kinase 3 beta (pGSK3β), throughout the menstrual cycle.

Results: Expression of Ki67 and SCF was higher in endometriosis than in control tissue (P < .05) and greater in secretory rather than proliferative (P < .01) endometrium in endometriosis. Expression of c-kit was also higher in endometriosis although similar in both phases. Expression of Akt and GSK3β was identical in all samples and cycle phases, whereas pAkt and pGSK3β, opposed to control tissue, remained overexpressed in the secretory phase in endometriosis.

Conclusion: Unceasing cell proliferation in the secretory phase of eutopic endometriosis is linked to deregulation of c-kit/SCF-associated signaling pathways.

Keywords: Akt/GSK3β; c-kit receptor; endometriosis; eutopic endometrium; stem cell factor.

MeSH terms

  • Adult
  • Biopsy
  • Case-Control Studies
  • Cell Proliferation*
  • Endometriosis / enzymology*
  • Endometriosis / pathology
  • Endometriosis / physiopathology
  • Endometrium / enzymology*
  • Endometrium / metabolism
  • Endometrium / pathology
  • Female
  • Glycogen Synthase Kinase 3 / analysis*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / analysis*
  • Proto-Oncogene Proteins c-kit / metabolism
  • Signal Transduction
  • Young Adult

Substances

  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-kit
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3