HL60 세포분화시 Rb 항암단백질과 세포주기조절인자들의 발현

Abstract

Differentiation will be divided into three general steps: cell cycle exit, apoptosis protection, and tissue-specific gene expression. The role of cell cycle control genes in the process of cell cycle exit is a largely unresolved issue. HL60 cells, a promyelocytic leukemia cell line, were differentiated into macrophage-like cells by 12-0-tetradecanoylphorbol-13-acetate (TPA). During TPA-induced HL60 cell differentiation, the expression patterns of the cell cycle control genes were investigated. The expression of hypophosphorylated Rb protein was remarkably increased compared with the control. Cyclin E and A proteins were dramatically decreased and cyclin- dependent kinase (CDK) 2 and 4 proteins were gradually decreased, but cyclin D1 proteins were gradually increased during differentiation. The expression of p21WAF1 was increased 1 day after TPA treatment and then remarkably up-regulated 2 days after TP A treatment. The expression of p27KIF1 was also remarkably up-regulated 1 day after TPA treatment. In conclusion, the increased expression of p21WAF1 and p27KIP1, and the decreased expression of cyclin E and A may cause the decreased activity of CDKs; and then hypophosphorylated Rb protein will be increased during the differentiation. The increased hypophosphorylated active Rb protein will stop the cells in G1 and produce proper conditions for cell cycle exit. Key Words: HL60 cell, Differentiation, Cell cycle control genes