Epigenetic silencing of cellular retinol-binding proteins in nasopharyngeal carcinoma
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AbstractAberrant 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.
All Author(s) ListKwong J, Lo KW, Chow LSN, To KF, Choy KW, Chan FL, Mok SC, Huang DP
Journal nameNeoplasia
Year2005
Month1
Day1
Volume Number7
Issue Number1
PublisherNEOPLASIA PRESS
Pages67 - 74
ISSN1522-8002
LanguagesEnglish-United Kingdom
KeywordsCRBPI; CRBPIV; hypermethylation; nasopharyngeal carcinoma; retinoid
Web of Science Subject CategoriesOncology; ONCOLOGY

Last updated on 2020-24-10 at 02:07