Ablation of CD24 inhibits proliferation of MCF-7 cells via negative modulation of MEK/ERK signaling

Abstract

Cluster of Differentiation 24 (CD24) functions as an adhesion molecule for P-selectin and is known to regulate metastasis in cancer. CD24 is expressed in a variety of human carcinomas, including epithelial breast cancer. In an attempt to determine the role of CD24 in cultured breast cancer cells, we knocked down CD24 in MCF-7 human breast cancer cell with retroviral delivery of shRNA. CD24 knocked-down MCF-7 (MCF-7 hCD24 shRNA) cells exhibited decreased cell proliferation and cell adhesion as compared to control MCF-7 mCD24 shRNA cells. Decreased proliferation of MCF-7 hCD24 shRNA cells was resulted from the inhibition of cell cycle progression from G1 to S phase. It appeared that the specific inhibition of MEK/ERK signaling by CD24 ablation is responsible for the down-regulation of cell proliferation. Studies using U0126, a specific inhibitor of MEK/ERK signaling revealed that treatment of MCF-7 mCD24 shRNA cells with U0126 with a dose that could down-regulate p-ERK level comparable to MCF-7 hCD24 shRNA resulted in a decreased proliferation of MCF-7 mCD24 shRNA cells with a rate similar to MCF-7 hCD24 shRNA cells. These results may suggest that down-regulation of MEK/ERK signaling is a major mechanism responsible for CD24 ablation-induced decrease in cell proliferation.