Discovery of Phosphatases Critical for the Growth and Tumorigenicity of ER-negative Breast Cancers
Supervised clustering of phosphatase genes that are differentially expressed in ER-positive and ER-negative breast cancer. The red box defines those phosphatases exhibiting higher expression levels in ER-negative versus ER-positive samples.
One of the goals of our lab is to define the phosphatases dysregulated in estrogen receptor (ER)-negative breast cancer. We have performed RNA gene profiling analysis of breast cancer samples obtained through a Susan G. Komen Promise grant (PI: Powel Brown). In one project, we compared phosphatase expression levels in ER-positive versus ER-negative breast cancers. Through this study, we have identified 276 phosphatase genes with differential expression levels in ER-negative breast cancers. We have determined that 20 of these phosphatases are expressed at levels ≥1.5-fold higher and 29 are expressed at levels ≤1.5-fold lower in ER-negative cancers compared to ER-positive cancers. Currently, we are focusing on those phosphatases over-expressed in ER-negative breast cancers and are testing whether knock-down of any of these phosphatases affects growth in soft agar and conventional cultures on plastic petri dishes, as well as in xenograft tumor models in nude mice. In the future, we will focus on determining those phosphatases critical for the induction and maintenance of ER-negative breast cancer by testing their ability to transform normal and pre-malignant cells and will investigate whether inhibitors of overexpressed phosphatases will be useful for the treatment of ER-negative breast cancer.
Lab members working on this project: