aberrant promoter cpg methylation is a mechanism for impaired phd3 expression in a diverse set of malignant cells异常的启动子cpg甲基化是一种机制,用于受损phd3表达式在各种恶性肿瘤细胞.pdfVIP

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aberrant promoter cpg methylation is a mechanism for impaired phd3 expression in a diverse set of malignant cells异常的启动子cpg甲基化是一种机制,用于受损phd3表达式在各种恶性肿瘤细胞.pdf

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Aberrant Promoter CpG Methylation Is a Mechanism for Impaired PHD3 Expression in a Diverse Set of Malignant Cells 1. 2. 3.¤ 4 Trenton L. Place , Matthew P. Fitzgerald , Sujatha Venkataraman , Sabine U. Vorrink , Adam J. 2 2 1,2,4,5 Case , Melissa L. T. Teoh , Frederick E. Domann * 1 Molecular and Cellular Biology Program, The University of Iowa, Iowa City, Iowa, United States of America, 2 Free Radical and Radiation Biology Program and Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa, United States of America, 3 University of Colorado Denver, Pediatrics, Aurora, Colorado, United States of America, 4 Human Toxicology Program, The University of Iowa, Iowa City, Iowa, United States of America, 5 Carver College of Medicine and The Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, Iowa, United States of America 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-a 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 proce