Dicer in Mammary Tumor Stem Cell Maintenance
Abstract
RNA interference (RNAi) is a gene silencing pathway with roles in mRNA stability, translational control, chromatin organization and genome regulation. MicroRNAs (miRNAs) are a set of small RNAs produced by the RNAi machinery that play important functions in tissue organization and maintenance of cell identity. Several miRNAs have been shown to collaborate with oncogenes in the progression of cancer, and in addition, miRNA expression profiling has revealed widespread miRNA misregulation in cancer. To address the role of miRNAs in the onset and maintenance of cancer, we have created embryonic stem (ES) cells and mice in which Dicer, a key enzyme in miRNA biogenesis, can be conditionally inactivated. We have demonstrated loss of Dicer delays onset of teratomas derived from subcutaneously injected ES cells. In addition, we have identified a miRNA family that is regulated by the master tumor-suppressor gene p53. We show that the miR-34 family is a direct target of p53 transcriptional regulation. Our work places miR-34 in the p53 tumor suppressor network, implicated in many cancers, including breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA469955
Entities
People
- Elizabeth P. Murchison
Organizations
- Cold Spring Harbor Laboratory