title: Increased expression of p21-activated kinase 4 in adenomyosis and its regulation of matrix metalloproteinase-2 and -9 in endometrial cells.
abstract: OBJECTIVE
  To investigate the expression of p21-activated kinase 4 (Pak4) in both adenomyotic foci and the eutopic endometrium of women with adenomyosis, and whether the activities of matrix metalloproteinases (MMPs)-2 and -9 are regulated by Pak4 in endometrial cells.
  
  
  METHODS
  Experimental study using human samples and cell lines.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Thirty-nine patients with histologic evidence of adenomyosis, and 34 patients with carcinoma in situ of the uterine cervix without adenomyosis or endometriosis.
  
  
  METHODS
  Immunohistochemistry, zymography after transfection with Pak4 small interfering RNA (siRNA), and western blot analyses after nuclear factor kappa-B (NF-кB) inhibitor treatment.
  
  
  METHODS
  The Pak4 immunoreactivity of women with vs. without adenomyosis was compared semiquantitatively. The activities of MMP-2 and -9 were analyzed in eutopic endometrial stromal cells and Ishikawa cells after transfection with Pak4 siRNA. The Pak4 expression was evaluated in endometrial cells after treatment with NF-кB inhibitor.
  
  
  RESULTS
  Pak4 immunoreactivity was increased in adenomyotic foci and in the eutopic endometrium of women with adenomyosis. Transfection of endometrial cells with Pak4 siRNA led to significant decreases of MMP-2 and -9 activities. In vitro treatment of endometrial cells with tumor necrosis factor-alpha caused a significant increase of NF-кB activation and Pak4 expression, which was obviously decreased by the NF-кB inhibitor pyrrolidinedithiocarbamate.
  
  
  CONCLUSIONS
  Our results suggest that Pak4 is regulated by NF-кB and that increased Pak4 expression can lead to development of adenomyosis by enhancing the invasiveness of endometrial cells through regulation of MMP-2 and -9 activities.
authors: Department of Obstetrics and Gynecology, College of Medicine, Korea University, Seoul, Republic of Korea.
authors: Kyong Wook
authors: KW
authors: Yi
authors: Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. Electronic address: kimsung@amc.seoul.kr.
authors: Sung Hoon
authors: SH
authors: Kim
authors: Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors: Hyo Jin
authors: HJ
authors: Ihm
authors: Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors: Young Sang
authors: YS
authors: Oh
authors: Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors: Hee Dong
authors: HD
authors: Chae
authors: Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors: Chung-Hoon
authors: CH
authors: Kim
authors: Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
authors: Byung Moon
authors: BM
authors: Kang
mesh_terms: D062788:Adenomyosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015854:Up-Regulation / Q000235:genetics; D054462:p21-Activated Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; C116367:PAK4 protein, human; D054462:p21-Activated Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: P21-activated kinase 4 (Pak4); adenomyosis; endometrium; matrix metalloproteinase (MMP); nuclear factor kappa-B (NF-кB)