Ser¹⁰ was the major phosphorylation site in p27^Kip1 (here after referred to as p27), accounting for 70% of the total phosphorylation of this protein, due to cytoplasmic shuttling. To further elucidate the mechanism for Ser¹⁰-mediated dysfunction of p27 during breast cancer progression. Affymetrix Human Genome U133A Array was used to identify differentially regulated genes between MCF-7 breast cancer cell lines stably-transfected with wild type and Ser¹⁰ mutant (substitution of Ser¹⁰ with Ala, S10A), alternatively. Then to confirm by RT-PCR then western blot partly. Microarray analysis showing that S10A, then abrogation of Ser¹⁰ phosphorylation, result in important changes in a large number of genes involved in the control of cell cycle, cell differentiation, metabolism, immune response and signal transduction. S10A induced cell cycle G₀ phase arrest by FACS method. And cell growth inhibition and abrogation of cytoplasmic translation. Our data indicate that abrogation of phosphorylation of Ser¹⁰ resulted in significant changes in gene expression profiles which mediate cell cycle redistribution, sub-cellular localization.