Identification of Wnt Receptors in Mammary Cells
Abstract
Over expression of Wnt proteins has long been know to lead to mammary hyperplasia and neoplasia in the mouse mammary gland. Unregulated Wnt signaling may also contribute to the formation of human breast tumours as over expression of Wnt proteins and nuclear localization of 13-catenin has been reported. The experiments in this proposal are designed to identify the receptor proteins responsible for transduction of oncogenic Wnt signals in mammary cells. Possible candidates are members of the Frizzled, Notch and LRP families of transmembrane proteins as all have been suggested to act as Wnt receptors. A survey of the Frizzled, Notch and LRP proteins expressed in the mature virgin mammary gland of the mouse has been conducted to identify candidate receptors. Currently the ability of these proteins to interact physically with Wnt ligands is being tested in cross- linking and co-immunoprecipitation experiments. Also the ability of these proteins to transduce, and of dominant negative form to attenuate, a Wnt signal is being evaluated in a functional assay for Wnt signaling. Finally, a mammary specific transgene encoding a dominant negative Wnt receptor has been produced. This will be introduced into mice by pronuclear injection and tested for its ability to antagonize extracellular Wnt signals in mice and to prevent the onset of mammary hyperplasia and tumorigenesis caused by the Wnt-1 oncogene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA389666
Entities
People
- Keith R. Brennan