The Role of Epigenetic Modifications in Retinoic Acid Receptor β2 Gene Expression in Human Prostate Cancers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2001-07

AUTHORS

Tsuyoshi Nakayama, Masatoshi Watanabe, Mikio Yamanaka, Yoshifumi Hirokawa, Hiroyoshi Suzuki, Haruo Ito, Ryuichi Yatani, Taizo Shiraishi

ABSTRACT

The retinoic acid receptor (RAR) beta gene is a putative tumor suppressor gene on chromosome 3p24, where a high incidence of loss of heterozygosity is detected in many types of tumors. Retinoic acid suppresses cancer cell growth through binding to RARs, especially RARbeta, indicating a critical role in mediating anticancer effects. Selective loss or down-regulation of RARbeta mRNA and protein has been reported in prostate cancers (PCas), although the mechanisms remain unclear. We investigated the role of epigenetic modification in RARbeta2 gene silencing. Aberrant methylation was detected in 11 of 14 (79%) primary PCas, 9 of 10 (90%) hormone-refractory PCas, and 2 of 4 (50%) PCa cell lines, but not in any normal prostate samples. Chromatin immunoprecipitation assay showed that all RARbeta2-negative cells (LNCaP, PC3, and DU145) were hypoacetylated at both histones H3 and H4. After exposure to 5-aza-2prime;-deoxycytidine treatment, Trichostatin A and all-trans retinoic acid induced partial demethylation, increased accumulation of acetylated histones, and markedly restored the expression of RARbeta2 in RARbeta2-negative cells. These data suggest that the RARbeta2 gene may be one of the frequently silenced genes by epigenetic modifications in PCa. More... »

PAGES

3780316

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/labinvest.3780316

    DOI

    http://dx.doi.org/10.1038/labinvest.3780316

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1026196224

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/11454993


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