nrf2 expression is regulated by epigenetic mechanisms in prostate cancer of tramp micenrf2表达式是由表观遗传机制在前列腺癌的流浪汉老鼠.pdfVIP

Nrf2 Expression Is Regulated by Epigenetic Mechanisms in Prostate Cancer of TRAMP Mice 1.¤ 1. 1 1 1 1 Siwang Yu , Tin Oo Khor , Ka-Lung Cheung , Wenge Li , Tien-Yuan Wu , Ying Huang , Barbara A. 2 3 1 Foster , Yuet Wai Kan , Ah-Ng Kong * 1 Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America, 2 Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, United States of America, 3 Cardiovascular Research Institute and Departments of Laboratory Medicine and Medicine, University of California San Francisco, San Francisco, California, United States of America Abstract Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is a transcription factor which regulates the expression of many cytoprotective genes. In the present study, we found that the expression of Nrf2 was suppressed in prostate tumor of the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. Similarly, the expression of Nrf2 and the induction of NQO1 were also substantially suppressed in tumorigenic TRAMP C1 cells but not in non-tumorigenic TRAMP C3 cells. Examination of the promoter region of the mouse Nrf2 gene identified a CpG island, which was methylated at specific CpG sites in prostate TRAMP tumor and in TRAMP C1 cells but not in normal prostate or TRAMP C3 cells, as shown by bisulfite genomic sequencing. Reporter assays indicated that methylation of these CpG sites dramatically inhibited the transcriptional activity of the Nrf2 promoter. Chromatin immunopreceipitation (ChIP) assays revealed increased binding of the methyl-CpG-bind