Investigating the Role of Hepatocyte Nuclear Factor-3 (HNF-3) Alpha and Beta in Prostate Cancer and Cellular Differentiation
Abstract
HNF-3 proteins are differentially expressed during mouse prostate development and we demonstrated, using knockout mice, that HNF-3alpha is necessary for normal prostate development. More recently, we showed that HNF-3 proteins are differentially expressed in transgenic mouse prostate cancer models. The aim of this project is to elucidate the role HNF-3 proteins play in prostate cancer cells by employing several molecular biological techniques; in vitro and in vivo models. Western blot analysis showed differential HNF-3 protein expression in human prostate cancer cells. Using tetracycline-regulated siRNAs targeted toward HNF-3alpha, I showed that decreased HNF-3alpha protein levels caused death of PC-3 cells. Overexpression of HNF-3alpha and beta had no effect on the in vitro proliferative index of DU-145 cells, but decreased proliferation of BPH-1 cells. BPH-1 cells overexpressing HNF-3 proteins were chosen for subsequent tissue recombinantion experiments. These in vivo experiments were performed in December 2004 and tissues will be harvested in the following weeks. We previously showed that HNF-3alpha interacts with the androgen receptor to regulate prostate specific gene transcription. STAT-3 binding sites also exist adjacent to HNF-3alpha on prostate specific promoters and I plan to perform experiments this year to determine how these two proteins interact to regulate
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2005
- Accession Number
- ADA431320
Entities
People
- Janni Mirosevich
Organizations
- Vanderbilt University