Epigenetic Alterations Associated with CCCTC-Binding Factor Deregulation in Prostate Cancer.

摘要

CCCTC-binding factor (CTCF) is a widely expressed 11-zinc finger nuclear protein. CTCF plays an important role in epigenetic regulation by establishing, maintaining epigenetic states in the genome, preventing the spread of DNA methylation, and maintaining methylation-free zones important in gene transcription. CTCF regulates multiple genes involved in cell cycle progression and growth deregulation in both normal and prostate cancer cells,. Thus, it serves as a master regulator that when functionally altered has the potential to globally change the behavior of a cell. It is our hypothesis that decreased CTCF expression in prostate cancer modulates the expression of growth promoting and tumor suppressor genes and may be an early permissive change in prostate cancer. Decreased CTCF expression would be associated with changes in local and global methylation especially at DNA binding sites of CTCF target genes in prostate cancer. Specific Aims: (1) Determine if decreased expression of CTCF leads to the deregulation of growth regulatory genes in human prostate epithelial cells and prostate cancer cells. (2) To test if decreased expression of CTCF leads to changes in local and global methylation. (3) Determine CTCF/BORIS expression or function in prostate cancer can predict clinical outcomes. To date, CTCF has not been examined in the context of prostate cancer and no studies have been done studying the effect of CTCF deregulation in normal or nontumorigenic cells. Given its role as a master regulator of multiple genes, this project has the potential to discover a new potential therapeutic target for future studies.