Abstract
ObjectiveTo investigate the effect of Lewis y overexpression on the expression of proliferation-related factors in ovarian cancer cells.MethodsmRNA levels of cyclins, CDKs, and CKIs were measured in cells before and after transfection with the α1,2-fucosyltransferase gene by real-time PCR, and protein levels of cyclins, CDKs and CKIs were determined in cells before and after gene transfection by Western blot.ResultsLewis y overexpression led to an increase in both mRNA and protein expression levels of cyclin A, cyclin D1 and cyclin E in ovarian cancer cells, decrease in both mRNA and protein expression levels of p16 and p21, and decrease of p27 at only the protein expression level without change in its mRNA level. There were no differences in proteins and the mRNA levels of CDK2, CDK4 and CDK6 before and after gene transfection. Anti-Lewis y antibody, ERK and PI3K pathway inhibitors PD98059 and LY294002 reduced the difference in cyclin and CKI expression caused by Lewis y overexpression.ConclusionLewis y regulates the expression of cell cycle-related factors through ERK/MAPK and PI3K/Akt signaling pathways to promote cell proliferation.
Highlights
Lewis y is a difucosylated oligosaccharide present on the surface of cells, and its expression is increased in many tumors
The percentage of RMG-IH cells in G1-phase after gene transfection were significantly reduced compared to either untransfected RMG-I or empty vector-transfected RMG-IM, while the corresponding percentages of cells in S and G2 phases were significantly increased. These results suggested that Lewis y overexpression, induced by α1,2-fucosyl-transferase gene transfection, promoted
cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CKIs) all play important roles in the cell cycle, so cell cycle factors closely related to G1/S phases were detected by the real-time PCR method
Summary
Lewis y is a difucosylated oligosaccharide present on the surface of cells, and its expression is increased in many tumors. Two kinds of CKI families have been found so far: one is the INK4 (an inhibitor of CDK4) protein family, including p15, p16, p18 and p19, where each of them contains four ankyrin repeats in its protein structure, mainly inhibiting the phosphorylation kinase activity of the cyclin D1-CDK4/6 complex; the other one is the CIP/KIP protein family, mainly including p21, p27 and p57, which have a nuclear localization signal (NLS) at the C-terminus, and a conserved region proximal to the amino-terminus. This group of proteins can exert their inhibitory activities by their interactions with a variety of cyclin-CDK complexes, and thereby induce S phase arrest [2,3,4]
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