CD24-Induced Regulation of Breast Cancer Cell Proliferation Is Mediated by Modulation of MEK/ERK Signaling

Abstract

Cluster of Differentiation 24 (CD24) is small, heavily mucin-type glycosylphosphatidylinositol (GPI)-linked cell surface molecule. CD24 is expressed on a variety of human carcinomas, including epithelial breast cancer and has been linked to poor prognosis. In an attempt to determine the role of CD24 in cultured breast cancer cells, we expressed CD24 in MDA-MB-231 cells (CD24 negative) using retroviral expression vector and knocked out CD24 in MCF-7 cells (CD24 positive) with siRNA. Forced expression of CD24 in MDA-MB-231 cells resulted in a decrease in MAPK phosphorylation and reduced cell proliferation. Interestingly, silencing of CD24 in MCF-7 cells also down-regulated MAPK phosphorylation and cell proliferation. These paradoxical results in two cell lines may suggest expression status of CD24 could affect intracellular signaling in cell type-specific manner. Currently, we are investigating the interplay of CD24 with other cell surface molecules in determining the intracellular signaling responses. The effect of CD24 expression on cell motility, resistance to anti-cancer drugs will also be discussed.