RNA-Binding Proteins as Novel Oncogenes and Tumor Suppressors in Breast Cancer

摘要

Post transcriptional control of gene expression is particularly important for oncoproteins and cell cycle proteins because their sustained synthesis favors cell growth rather than differentiation, a hallmark of the neoplastic phenotype. Control is exerted via the opposing actions of the RNA- binding proteins AUF1 and HuR. AUF1 triggers degradation of mRNA subsets while HuR promotes mRNA stabilization. Phase I of this work is to examine the effects of AUF1 and HuR expression levels on global gene expression in human breast carcinoma cells. Phase II is to assess roles of AUF1 and HuR in cellular proliferation and tumorigenesis in vivo. Previously, we discovered that AUF1 knockdown elevates expression of c-myc proto-oncogene by in vivo association with the mRNA, accelerates breast cancer cell proliferation, and alters their cell-cell adhesion properties. To explain the biological effects of AUF1 knockdown, we performed cDNA microarray analyses during the final funding period to identify AUF1's target mRNA subsets and their regulation by AUF1.