RNA-Binding Proteins as Novel Oncogenes and Tumor Suppressors in Breast Cancer
Abstract
The level of an mRNA depends upon its relative rates of synthesis and degradation. This 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. This control is exerted via a balance between the action of at least two RNA-binding proteins, AUF1 and HuR. AUF1 targets the degradation of mRNAs like the c-myc proto-oncogene and the cell cycle regulator cyclin D1. By contrast, HuR promotes stabilization of mRNAs. c-myc and cyclin D1 are particularly important, since both play causative roles in mammary tumorigenesis. 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 the roles of AUF1 and HuR in cellular proliferation and tumorigenesis in vivo. During this funding period, we continued Phase I by transfecting expression vectors for inducible overexpression or knocked-down expression of AUF1 or HuR in human breast carcinoma cells and selecting a panel of clones. We also began identification of transcripts that are binding targets of AUF1 using mRNP immunoprecipitation (RIP) and cDNA microarray analyses of purified mRNAs.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2005
- Accession Number
- ADA474438
Entities
People
- Gary Brewer
Organizations
- Robert Wood Johnson Medical School