Epigenetic Control of Prolyl and Asparaginyl Hydroxylases in Prostate Cancer

摘要

In many solid tumors, including prostate cancer, hypoxia-inducible factors (HIF) are up-regulated compared to their normal tissue counterparts. These HIF molecules are transcription factors, and up-regulate metabolic and angiogenic proteins in the cancer. Recently, a set of proteins known as prolyl and asparaginyl hydroxylases (PHD and AHD respectively) have been shown to be essential in the regulation of HIF, and in some cancers have been transcriptionally and translationally silenced. We therefore proposed a study that focuses on the epigenetic control of these crucial enzymes. In this report, we present data demonstrating our first findings of PHD expression in prostate cancer cell lines as well as expanding our studies to relevant human samples. Furthermore, we begin to identify specific epigenetic mechanisms that may play a major role in the transcriptional and translational control of these enzymes. Last, we will explain our future direction of the project after the award period has expired.