title: Lewis y antigen promotes the proliferation of ovarian carcinoma-derived RMG-I cells through the PI3K/Akt signaling pathway.
abstract: BACKGROUND
  Lewis y antigen is difucosylated oligosaccharide and is carried by glycoconjugates at cell surface. Elevated expression of Lewis y has been found in 75% of ovarian tumor, and the high expression level is correlated to the tumor's pathological staging and prognosis. This study was to investigate the effect and the possible mechanism of Lewis y on the proliferation of human ovarian cancer cells.
  
  
  METHODS
  We constructed a plasmid encoding alpha1,2-fucosyltransferase (alpha1,2-FT) gene and then transfected it into ovarian carcinoma-derived RMG-I cells with lowest Lewis y antigen expression level. Effect of Lewis y on cell proliferation was assessed after transfection. Changes in cell survival and signal transduction were evaluated after alpha-L-fucosidase, anti-Lewis y antibody and phosphatidylinositol 3-kinase (PI3K) inhibitor treatment.
  
  
  RESULTS
  Our results showed that the levels of alpha1,2-FT gene and Lewis y increased significantly after transfection. The cell proliferation of ovarian carcinoma-derived RMG-I cells sped up as the Lewis y antigen was increased. Both of alpha-L-fucosidase and anti-Lewis y antibody inhibited the cell proliferation. The phosphorylation level of Akt was apparently elevated in Lewis y-overexpressing cells and the inhibitor of PI3K, LY294002, dramatically inhibited the growth of Lewis y-overexpressing cells. In addition, the phosphorylation intensity and difference in phosphorylation intensity between cells with different expression of alpha1,2-FT were attenuated significantly by the monoantibody to Lewis y and by the PI3K inhibitor LY294002.
  
  
  CONCLUSIONS
  Increased expression of Lewis y antigen plays an important role in promoting cell proliferation through activating PI3K/Akt signaling pathway in ovarian carcinoma-derived RMG-I cells. Inhibition of Lewis y expression may provide a new therapeutic approach for Lewis y positive ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, China Medical University Shengjing, Hospital, 36 Sanhao Street, Heping, Shenyang, 110004, PR China. juanjuanliu_lg@yahoo.com.cn
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Liu
authors.forename: Bei
authors.initials: B
authors.lastname: Lin
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hao
authors.forename: Yue
authors.initials: Y
authors.lastname: Qi
authors.forename: Liancheng
authors.initials: L
authors.lastname: Zhu
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.forename: Dawo
authors.initials: D
authors.lastname: Liu
authors.forename: Jianping
authors.initials: J
authors.lastname: Cong
authors.forename: Shulan
authors.initials: S
authors.lastname: Zhang
authors.forename: Masao
authors.initials: M
authors.lastname: Iwamori
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005647:Fucosyltransferases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007983:Lewis Blood Group Antigens / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D004791:Enzyme Inhibitors; D005647:Fucosyltransferases; D007983:Lewis Blood Group Antigens; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000097631:Galactoside 2-alpha-L-fucosyltransferase; C094162:Lewis Y antigen