Accession Number : ADA462567


Title :   Dicer in Mammary Tumor Stem Cell Maintenance


Descriptive Note : Annual summary rept. 15 Feb 2005-14 feb 2006


Corporate Author : COLD SPRING HARBOR LAB NY


Personal Author(s) : Murchison, Elizabeth P


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a462567.pdf


Report Date : Mar 2006


Pagination or Media Count : 9


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 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.


Descriptors :   *ENZYMES , *BREAST CANCER , *STEM CELLS , MAINTENANCE , MODEL TESTS , GENES , CLONES , GENETIC ENGINEERING , EMBRYOS , GENOME , CELLS(BIOLOGY) , RIBONUCLEIC ACIDS , TRANSPLANTATION , MAMMARY GLANDS , GROWTH(PHYSIOLOGY) , CHROMATIN , ONCOGENIC VIRUSES


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE