Lewis y antigen promotes the proliferation of ovarian carcinoma-derived RMG-I cells through the PI3K/Akt signaling pathway.
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.
Liu
Juanjuan
J
Department of Obstetrics and Gynecology, China Medical University Shengjing, Hospital, 36 Sanhao Street, Heping, Shenyang, 110004, PR China. juanjuanliu_lg@yahoo.com.cn
Lin
Bei
B
Hao
Yingying
Y
Qi
Yue
Y
Zhu
Liancheng
L
Li
Feifei
F
Liu
Dawo
D
Cong
Jianping
J
Zhang
Shulan
S
Iwamori
Masao
M
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
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