title: Regulation of P21-activated kinase-4 by progesterone and tumor necrosis factor-α in human endometrium and its increased expression in advanced-stage endometriosis.
abstract: BACKGROUND
  Endometriosis is a common gynecological condition characterized by enhanced proliferation, adhesiveness, invasiveness, and survival of endometrial cells after retrograde menstruation. Originally identified as a cytoskeletal regulatory kinase, p21-activated kinase 4 (Pak4) regulates diverse cellular activities that might be altered in the establishment and progression of endometriosis.
  
  
  OBJECTIVE
  The aim was to evaluate the effects of sex steroids and proinflammatory cytokines on the Pak4 expression in endometrial cells along with the functional change caused by inhibition of Pak4 expression as well as to see whether the Pak4 expression is altered in endometriosis.
  
  
  METHODS
  Pak4 expression was analyzed using immunohistochemistry and Western blot analysis. Viability and invasiveness were assayed after transfection of endometrial cells with Pak4 small interfering RNA.
  
  
  RESULTS
  The Pak4 expression was significantly decreased in the stromal cells during the secretory phase as well as by in vitro treatment with progesterone. The immunoreactivity of Pak4 was significantly increased in the eutopic endometrium as well as in the ovarian endometriotic cyst of women with endometriosis compared with the control subjects. TNF-α induced a significant increase in the Pak4 expression in endometrial cells in vitro, whereas IL-1β had no effects. Transfection of endometrial cells with Pak4 small interfering RNA led to a significant decrease in viability and invasiveness in endometrial cells.
  
  
  CONCLUSIONS
  These findings suggest that Pak4 is regulated by progesterone and TNF-α in endometrial cells and that the increased expression of Pak4 might lead to the establishment and progression of endometriosis by enhanced cellular viability and invasiveness in endometrial cells.
authors.affiliation: MD, PhD, Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, 388-1, Pungnap-2dong, Songpa-gu, Seoul 138-736, Korea. kimsung@amc.seoul.kr
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: So Ra
authors.initials: SR
authors.lastname: Kim
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Ihm
authors.forename: Young Sang
authors.initials: YS
authors.lastname: Oh
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Chae
authors.forename: Chung-Hoon
authors.initials: CH
authors.lastname: Kim
authors.forename: Byung Moon
authors.initials: BM
authors.lastname: Kang
mesh_terms: D000328:Adult; D002460:Cell Line; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010049:Ovarian Diseases / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone; D054462:p21-Activated Kinases