Epigenetic silencing of cellular retinol-binding proteins in nasopharyngeal carcinoma
Publication in refereed journal


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摘要Aberrant retinoid signaling in human cancers is extending from the nucleus to the cytoplasm. Recently, we have demonstrated frequent epigenetic inactivation of a retinoic acid receptor (RAR), RARbeta2, in nasopharyngeal carcinoma (NPC). To further explore targets contributing to aberrant retinoid signaling in NPC, the expression of cellular retinol-binding proteins (CRBPs), cellular retinoic acid-binding proteins (CRABPs), RARs, and retinoid X receptors (RXRs) was examined. Apart from RARbeta2, transcriptional silencing of two CRBPs, CRBPI and CRBPIV, was observed in NPC cell lines and xenografts. Hypermethylation of CRBPI and CRBPIV CpG islands was found to be closely correlated with the loss of expression. Treatment with the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, resulted in reexpression of CRBPI and CRBPIV gene expression in NPC cell lines. Both CRBPI and CRBPIV hypermethylations were also observed in 43/48 (87.8%) and 26/48 (54.2%) primary NPC tumors, respectively. Here, we reported for the first time that CRBPIV was transcriptionally inactivated by promoter, hypermethylation in human cancer. Simultaneous methylation of CRBPI, CRBPIV, and RARbeta2 was commonly found in NPC primary tumors. Our findings implied that epigenetic disruption of the CRBPs, CRBPI and CRBPIV, is important in NPC tumorigenesis and may contribute to the loss of retinoic acid responsiveness in cancer.
著者Kwong J, Lo KW, Chow LSN, To KF, Choy KW, Chan FL, Mok SC, Huang DP
期刊名稱Neoplasia
出版年份2005
月份1
日期1
卷號7
期次1
出版社NEOPLASIA PRESS
頁次67 - 74
國際標準期刊號1522-8002
語言英式英語
關鍵詞CRBPI; CRBPIV; hypermethylation; nasopharyngeal carcinoma; retinoid
Web of Science 學科類別Oncology; ONCOLOGY

上次更新時間 2020-26-11 於 01:25