Variation of gene expression profile linked to p27 (Kip1) Ser(10) phosphorylation status in MCF-7 cell line

Abstract

Ser(10) 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 Ser(10)-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 Ser(10) mutant (substitution of Ser(10) with Ala, S10A), alternatively. Then to confirm by RT-PCR then western blot partly. Microarray analysis showing that S10A, then abrogation of Ser(10) 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 G(0) phase arrest by FACS method. And cell growth inhibition and abrogation of cytoplasmic translation. Our data indicate that abrogation of phosphorylation of Ser(10) resulted in significant changes in gene expression profiles which mediate cell cycle redistribution, sub-cellular localization.