Mechanism of Prostate Cancer Prevention by Down-Regulation of the GH/IGF Axis
Abstract
The purpose of this project was to test the hypothesis that growth hormone (GH) stimulates specific pathways, some of which are independent of IGF-I, for promoting proliferation and inhibiting death in prostate cancer cells. Our first aim is to determine which of the multiple signaling pathways stimulated by GH receptor are required to promote prostate cancer. Our strategy was to cross mice that develop prostate cancers due to a large T antigen (TAg) transgene with mice that lack discrete segments of the intracellular portion of the GH receptor. We have not yet completed this experiment due to insufficient breeder fecundity. To assess the relative contribution of IGF-I and GH to prostate carcinogenesis, we grafted prostate tissue harboring the TAg transgene. The grafts were either Ghr+/+ or Ghr-/- and therefore were able to respond to IGF-I but not detect GH. Our results suggest that IGF-I is the major driver of carcinogenesis. We also planned to propagate human prostate cancer cells in vitro and expose them to a human growth hormone antagonist. In vitro, however, the cells were neither stimulated by recombinant human GH nor inhibited by GH antagonist.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA566644
Entities
People
- Steven M. Swanson
Organizations
- University of Chicago