Hedgehog Signal Transduction Inhibitors in Breast Cancer Treatment and Prevention
Abstract
Mutations in at least two hedgehog signal transduction network genes lead to defects in mammary gland development. These mutations can cause enhanced hedgehog signaling in some organs. If this mechanism is functioning in the mammary gland, defects should be inhibited or reverted by treatment with specific inhibitors of hedgehog signaling. One such inhibitor is called cyclopamine which causes birth defects in sheep when ingested during pregnancy. We are using slow-release pellets containing cyclopamine to test whether developmental defects can inhibit or revert defects caused by mutations in the hedgehog network. These mutations include null alleles for Ptcl and Gli2 as well as a constitutively activated form of Smo. As controls we are also testing the in vivo effect of cyclopamine treatment on preneoplastic growths presumably caused by genetic alterations independent of hedgehog signaling. The effect of cyclopamine on normal mammary development and function is also being examined. Finally, we are testing the effect of cyclopamine on a series of human mammary epithelial cell lines for changes in their growth behavior. if cyclopamine can slow or prevent neoplastic growth, this class of inhibitors may be useful in breast cancer treatment or prevention
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA398338
Entities
People
- Michael T. Lewis
Organizations
- University of Colorado Health