Wnt-1 is a mammary oncogene which causes hyperplasia and tumorigenesis when activated in mouse mammary gland and causes transformation of certain mammary epithelial cells in culture. The gene normally functions in fetal brain morphogenesis. Wnt-1 encodes a secreted protein that acts in cell-cell signalling. The goal of this research proposal is to investigate the mechanism of action of Wnt-1 in mammary cell transformation, using two recently identified sources of soluble Wnt-1 proteins. The active form of Wnt-1 protein and any associated factors will be characterized, and used to investigate early molecular responses to Wnt-1 in mammary cells, and to identify and characterize Wnt receptors. The effects of Wnt signals on plakoglobin and beta-catenin will be evaluated, as well as other mammalian homologs of components of the putative Wnt-1 signaling pathway in Drosophila. Proteins that are rapidly tyrosine phosphorylated in response to Wnt-1 will be characterized. Radiolabeled Wnt-1 will be used to demonstrate specific binding to cells and to identify receptors by cross-linking and affinity labeling.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA047207-09
Application #
2837627
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Freeman, Colette S
Project Start
1988-04-01
Project End
2000-11-30
Budget Start
1998-12-01
Budget End
1999-11-30
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
Gray, Jason D; Kholmanskikh, Stanislav; Castaldo, Bozena S et al. (2013) LRP6 exerts non-canonical effects on Wnt signaling during neural tube closure. Hum Mol Genet 22:4267-81
Masckauchan, T Nestor H; Agalliu, Dritan; Vorontchikhina, Marina et al. (2006) Wnt5a signaling induces proliferation and survival of endothelial cells in vitro and expression of MMP-1 and Tie-2. Mol Biol Cell 17:5163-72
Ai, Z; Fischer, A; Spray, D C et al. (2000) Wnt-1 regulation of connexin43 in cardiac myocytes. J Clin Invest 105:161-71
Shimizu, H; Julius, M A; Giarre, M et al. (1997) Transformation by Wnt family proteins correlates with regulation of beta-catenin. Cell Growth Differ 8:1349-58