Aberrant promoter CpG methylation is a mechanism for impaired PHD3 expression in a diverse set of malignant cells.

ABSTRACT:

Background

The prolyl-hydroxylase domain family of enzymes (PHD1-3) plays an important role in the cellular response to hypoxia by negatively regulating HIF-α proteins. Disruption of this process can lead to up-regulation of factors that promote tumorigenesis. We observed decreased basal expression of PHD3 in prostate cancer tissue and tumor cell lines representing diverse tissues of origin. Furthermore, some cancer lines displayed a failure of PHD3 mRNA induction when introduced to a hypoxic environment. This study explores the mechanism by which malignancies neither basally express PHD3 nor induce PHD3 under hypoxic conditions.

Methodology/principal findings

Using bisulfite sequencing and methylated DNA enrichment procedures, we identified human PHD3 promoter hypermethylat

SUBMITTER: Place TL 

PROVIDER: S-EPMC3030558 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature