title: JNK suppression is essential for 17β-Estradiol inhibits prostaglandin E2-Induced uPA and MMP-9 expressions and cell migration in human LoVo colon cancer cells.
abstract: BACKGROUND
  Epidemiological studies demonstrate that the incidence and mortality rates of colorectal cancer in women are lower than in men. However, it is unknown if 17β-estradiol treatment is sufficient to inhibit prostaglandin E2 (PGE2)-induced cellular motility in human colon cancer cells.
  
  
  METHODS
  We analyzed the protein expression of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), matrix metallopeptidases (MMPs), plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinases (TIMPs), and the cellular motility in PGE2-stimulated human LoVo cells. 17β-Estradiol and the inhibitors including LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), QNZ (NFκB inhibitor) and ICI 182 780 were further used to explore the inhibitory effects of 17β-estradiol on PGE2-induced LoVo cell motility. Student's t-test was used to analyze the difference between the two groups.
  
  
  RESULTS
  Upregulation of urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and matrix metallopeptidases (MMPs) is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor. After administration of inhibitors including LY294002, U0126, SB203580, SP600125 or QNZ, we found that PGE2 treatment up-regulated uPA and MMP-9 expression via JNK1/2 signaling pathway, thus promoting cellular motility in human LoVo cancer cells. However, PGE2 treatment showed no effects on regulating expression of tPA, MMP-2, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloproteinase-1, -2, -3 and -4 (TIMP-1, -2, -3 and -4). We further observed that 17β-estradiol treatment inhibited PGE2-induced uPA, MMP-9 and cellular motility by suppressing activation of JNK1/2 in human LoVo cancer cells.
  
  
  CONCLUSIONS
  Collectively, these results suggest that 17β-estradiol treatment significantly inhibits PGE2-induced motility of human LoVo colon cancer cells.
authors.affiliation: 1Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Hsi-Hsien
authors.initials: HH
authors.lastname: Hsu
authors.forename: Wei-Syun
authors.initials: WS
authors.lastname: Hu
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: Li-Mien
authors.initials: LM
authors.lastname: Chen
authors.forename: Wei-Kung
authors.initials: WK
authors.lastname: Chen
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Hwang
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Liu
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D015232:Dinoprostone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D019714:Tissue Inhibitor of Metalloproteinases; D004958:Estradiol; D048055:Mitogen-Activated Protein Kinase 8; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone