lewisy抗原通过PI3K/Akt信号通路促进卵巢癌RMG-I细胞增殖。

PubMed ID
发表日期 2009年Dec月

原始出处 实验与临床癌症研究杂志
Journal of experimental & clinical cancer research : CR
作者 Liu  Juanjuan  Lin  Bei  Hao  Yingying  Qi  Yue  Zhu  Liancheng  Li  Feifei  Liu  Dawo  Cong  Jianping  Zhang  Shulan  Iwamori  Masao 

文献标题 lewisy抗原通过PI3K/Akt信号通路促进卵巢癌RMG-I细胞增殖。
Lewis y antigen promotes the proliferation of ovarian carcinoma-derived RMG-I cells through the PI3K/Akt signaling pathway.

文献摘要 BACKGROUND

lewisy抗原是二岩藻糖基化的寡糖,由细胞表面的糖缀合物携带。lewisy在75%的卵巢肿瘤中有高表达,其高表达水平与肿瘤的病理分期及预后有关。本研究旨在探讨lewisy对人卵巢癌细胞增殖的影响及其可能机制。

METHODS

我们构建了编码α1,2-岩藻糖基转移酶(alpha1,2-FT)基因的质粒,并将其转染到lewisy抗原表达水平最低的卵巢癌RMG-I细胞中。转染后观察lewisy对细胞增殖的影响。在α-L-岩藻糖苷酶、抗Lewis y抗体和磷脂酰肌醇3-激酶(PI3K)抑制剂处理后评估细胞存活和信号转导的变化。

RESULTS

结果表明,转染后alpha1,2-FT基因和lewisy水平显著升高。随着lewisy抗原的增加,卵巢癌RMG-I细胞的增殖速度加快。α-L-岩藻糖苷酶和抗Lewis y抗体均能抑制细胞增殖。lewisy过表达细胞Akt磷酸化水平明显升高,PI3K抑制剂LY294002显著抑制lewisy过表达细胞的生长。此外,lewisy单抗和PI3K抑制剂LY294002可显著减弱α1,2-FT不同表达细胞间的磷酸化强度和磷酸化强度差异。

CONCLUSIONS

lewisy抗原的表达增强通过激活PI3K/Akt信号通路在卵巢癌RMG-I细胞中发挥重要作用。抑制lewisy表达可能为lewisy阳性卵巢癌的治疗提供新的途径。


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.


获取全文 10.1186/1756-9966-28-154