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Epigenetic DNA Methylation of Anti-oxidative Stress Regulator NRF2 in Human Prostate Cancer
Khor, Tin Oo; Fuentes, Francisco; Shu, Limin; Paredes-Gonzalez, Ximena; Yang, Anne Yuqing; Liu, Yue; Smiraglia, Dominic J.; Yegnasubramanian, Srinivasan; Nelson, William G.; Kong, Ah-Ng Tony
Abstract:
Epigenetic control of NRF2, a master regulator of many critical anti-oxidative stress defense genes in human prostate cancer (CaP) is unknown. Our previous animal study found decreased Nrf2 expression through promoter CpG methylation/histone modifications during CaP progression in TRAMP mice. In this study, we evaluated CpG methylation of human NRF2 promoter in 27 clinical CaP samples and in LNCaP cells using MAQMA analysis and bisulfite genomic DNA sequencing. Prostate cancer tissue microarray (TMA) containing normal and prostate cancer tissues were studied by immunohistochemistry. Luciferase reporter assay using specific human NRF2 DNA promoter segments and ChIP assay against histone modifying proteins were performed in LNCaP cells. Three specific CpG sites in the NRF2 promoter were found to be hypermethylated in clinical CaP samples (BPH<ADT-RCaP
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