Despite high concentrations in females, no clear biological function has been attributed to reduced progesterone metabolites. However, recent evidence ties progesterone metabolites to selective modulation of breast cancer cell proliferation by binding novel steroid receptors on cell surface. Current methods do not allow for the selective targeting of these putative receptors. The hypothesis of this proposal is that cell membrane impermeable analogues of these progesterone metabolites will allow for selective modulation of their putative receptor and allow for further characterization of this potential new drug target for the treatment of breast cancer. This proposal will specifically focus on three experimental objectives: 1) Design and synthesize progesterone metabolites attached to a synthetic polymer chain to selectively target putative receptors on cell surface. 2) Determine the ability of these pregnane derivatized polymers to modulate the cell proliferation of breast cancer cell lines. 3) Use the pregnane derivatized polymers and small molecule libraries to assess the molecular determinants of the modulation of cancer cells by receptor and its ligands.
| Trebley, J P; Rickert, E L; Reyes, P T et al. (2006) Tamoxifen-based probes for the study of estrogen receptor-mediated transcription. Ernst Schering Res Found Workshop :75-87 |
