Abstract: Objective: To investigate the effect of Lewis y overexpression on the expression of proliferation-related factors in ovarian cancer cells. Methods: mRNA 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. Results: Lewis 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. Conclusion: Lewis y regulates the expression of cell cycle-related factors through ERK/MAPK and PI3K/Akt signaling pathways to promote cell proliferation.
Keywords: Lewis(y) antigen; cell cycle; cyclin; cyclin-dependent kinases; cyclin-dependent kinase inhibitors
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Liu, D.; Liu, J.; Lin, B.; Liu, S.; Hou, R.; Hao, Y.; Liu, Q.; Zhang, S.; Iwamori, M. Lewis y Regulate Cell Cycle Related Factors in Ovarian Carcinoma Cell RMG-I in Vitro via ERK and Akt Signaling Pathways. Int. J. Mol. Sci. 2012, 13, 828-839.
Liu D, Liu J, Lin B, Liu S, Hou R, Hao Y, Liu Q, Zhang S, Iwamori M. Lewis y Regulate Cell Cycle Related Factors in Ovarian Carcinoma Cell RMG-I in Vitro via ERK and Akt Signaling Pathways. International Journal of Molecular Sciences. 2012; 13(1):828-839.
Liu, Dawo; Liu, Juanjuan; Lin, Bei; Liu, Shuice; Hou, Rui; Hao, Yingying; Liu, Qing; Zhang, Shulan; Iwamori, Masao. 2012. "Lewis y Regulate Cell Cycle Related Factors in Ovarian Carcinoma Cell RMG-I in Vitro via ERK and Akt Signaling Pathways." Int. J. Mol. Sci. 13, no. 1: 828-839.