Repression of CD44 expression by p53 in a breast cancer progression model

[[abstract]]CD44 is an important molecule in breast cancer. Although CD44 lacks its own signaling domain, it can associate with and co-stimulate signaling by a number of growth factor receptors, such as Her2 and EGF receptor 1. Knockdown of CD44 significantly reduces mammary tumor-initiating frequency and tumor weight. Disruption of tumor cell surface CD44 function induces apoptosis in metastatic mammary carcinoma cells in vivo. Some studies showed that the breast cancer stem cells are enriched in the CD44highCD24low population. The tumor suppressor p53 is mutated or functionally inactivated in over 70% of cancer. In breast cancer, p53 is mutated in ~35% cases, and ~50% breast cancers contain MDM2 or MDMX overexpression. A previous study showed that p53 repressed the expression of CD44 and that this activity was essential for the tumor-suppressor function of p53. We find that p53 potently represses the expression of CD44 in normal human breast epithelial cells. Mutation of the p53 binding site on the CD44 promoter greatly reduces the ability of p53 to repress CD44 expression. We show that p53 repression of CD44 expression is progressively reduced in a breast cancer progression model. Our ongoing studies are elucidating the underlying mechanisms. Our findings will help for better understanding and treatment of breast cancer