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    Expression of RFG/ELE1alpha/ARA70 in normal and malignant prostatic epithelial cell cultures and lines: regulation by methylation and sex steroids

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    Authors
    Tekur, Seshadri
    Lau, Kin-Mang
    Long, John P.
    Burnstein, Kerry L.
    Ho, Shuk-Mei
    UMass Chan Affiliations
    Department of Surgery, Division of Urology
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    2001-03-20
    Keywords
    Androgens; Base Sequence; Chromosome Mapping; Chromosomes, Human, Pair 5; *DNA Methylation; DNA Primers; Epithelial Cells; Estrogens; Gene Expression Regulation, Neoplastic; Humans; Male; Prostate; Prostatic Neoplasms; Recombinant Fusion Proteins; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured
    Life Sciences
    Medicine and Health Sciences
    
    Metadata
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    Link to Full Text
    http://dx.doi.org/10.1002/1098-2744(200101)30:1<1::AID-MC1008>3.0.CO;2-X
    Abstract
    RET fused gene (RFG)/ELE1alpha/androgen receptor-associated protein 70(ARA70) was first found to be involved in the activation of the RET proto-oncogene in thyroid neoplasm and has recently been shown to be a ligand-dependent transcriptional coregulator for androgen receptor (AR). The functionality of RFG/ELE1alpha/ARA70 remains controversial, and little is known about factors regulating its expression in the prostate. Of significant interest is whether this molecule is involved in prostate carcinogenesis. Using reverse transcriptase-polymerase chain reaction semiquantitation, we compared RFG/ELE1alpha/ARA70 mRNA levels in four prostate cancer cell lines (LNCaP, TSU-Pr1, DU-145, and PC-3) with those found in primary cultures of normal prostatic epithelial cells (PrECs). In addition, we examined the effects of androgen and antiandrogen, estrogen and antiestrogen, and a demethylating agent on RFG/ELE1alpha/ARA70 mRNA expression levels in AR- and AR+ PC-3 cells. Reduced levels of RFG/ELE1alpha/ARA70 message were observed in all four prostate cancer cell lines when compared with normal PrECs in primary cultures. RFG/ELE1alpha/ARA70 mRNA levels in PC-3 cells, which express both estrogen receptor subtypes, were upregulated by 17beta-estradiol and inhibited by the antiestrogen ICI-182780. In PC-3(AR+) cells, which were genetically engineered to express AR, exposure to androgen upregulated RFG/ELE1alpha/ARA70 mRNA expression, whereas treatment with 4-hydroxyflutamide lowered expression of this transcript. Furthermore, treatment of DU-145 cells, which did not express RFG/ELE1alpha/ARA70 transcripts, with a demethylating agent reactivated transcription of this gene. Polymerase chain reaction analyses of monochromosomal human-rodent hybrid panels localized a putative RFG/ELE1alpha/ARA70 isoform on human chromosome 5q31.1-31.2. In summary, we identified sex hormones and DNA hypermethylation as regulators of RFG/ELE1alpha/ARA70 expression in prostate cancer cells. In addition, we found reduced levels of RFG/ELE1alpha/ARA70 expression in prostate cancer cell lines when compared with expression levels in normal PrECs in culture. These findings suggest that RFG/ELE1alpha/ARA70 may be involved prostate carcinogenesis and that it may serve as a key mediator of estrogen-androgen synergism.
    Source
    Mol Carcinog. 2001 Jan;30(1):1-13.
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32680
    PubMed ID
    11255259
    Related Resources
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    Morningside Graduate School of Biomedical Sciences Scholarly Publications

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