Selective blockade of prostaglandin E2 receptors EP2 and EP4 signaling inhibits proliferation of human endometriotic epithelial cells and stromal cells through distinct cell cycle arrest. Academic Article uri icon

abstract

  • OBJECTIVE: To determine interactions between prostaglandin (PG) E(2) signaling and proliferation of endometriotic cells to increase our knowledge about PGE(2) signaling in the pathogenesis of endometriosis in humans. DESIGN: Immortalized human endometriotic epithelial and stromal cells were used as an in vitro model. Effects of inhibition of PGE(2) receptors on proliferation of endometriotic cells and associated cell cycle regulation were determined. SETTING: College Veterinary Medicine and Biomedical Sciences, Texas A&M University. PATIENT(S): Not available. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cell proliferation, cell viability, cell cycle, regulation of cyclins, cyclin-dependent kinases, and cyclin-dependent kinase inhibitors. RESULT(S): Selective blockade of EP2/EP4 inhibited proliferation of human endometriotic cells by inducing cell cycle arrest at the G(1)-S and G(2)-M checkpoints in epithelial cells and at the G(2)-M checkpoint in stromal cells. This cell cycle arrest during specific checkpoints was associated with distinct regulation of respective cyclins and cyclin-dependent kinases. Inhibition of EP1 did not decrease endometriotic cell proliferation. CONCLUSION(S): For the first time data from the present study provide a direct molecular link between PGE(2) signaling and proliferation of endometriotic cells and suggest that inhibition of EP2/EP4 could be a potential nonestrogen (E) treatment option for endometriosis in women.

published proceedings

  • Fertil Steril

altmetric score

  • 4

author list (cited authors)

  • Lee, J., Banu, S. K., Rodriguez, R., Starzinski-Powitz, A., & Arosh, J. A.

citation count

  • 28

complete list of authors

  • Lee, JeHoon||Banu, Sakhila K||Rodriguez, Royce||Starzinski-Powitz, Anna||Arosh, Joe A

publication date

  • January 2010