Dicer in Mammary Tumor Stem Cell Maintenance
Annual summary rept. 15 Feb 2005-14 feb 2006
COLD SPRING HARBOR LAB NY
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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 breast cancer, we have created embryonic stem ES cells and mice in which Dicer, a key enzyme in miRNA biogenesis, can be conditionally inactivated. Using these systems we have demonstrated that Dicer is required for the continued proliferation of ES cells, and that there is indeed a loss of all miRNAs and RNAi-related functions in Dicer null cells. We are using a transplantation model to test the requirement of Dicer for the proliferation of mammary stem cells, and in addition we are cloning small RNAs from mammary stem cells in order to determine the regulatory niches that miRNAs may fill in this cell type. Our ultimate goal is to assess the role of Dicer in mammary tumor stem cell maintenance.
- Anatomy and Physiology
- Medicine and Medical Research