Cell cycle regulated expression of NCoR might control cyclic expression of androgen responsive genes in an immortalized prostate cell line.
In this work we have studied the mechanisms of regulation of expression of androgen receptor (AR) target genes. We have used an immortalized non-tumorigenic prostate cell line RWPE-1-AR(tag) constitutively expressing an exogenous AR as a model. We observed that all studied AR target genes exhibited a specific expression during the G1 phase of the cell cycle despite the constitutive expression of AR. Importantly, we found that the expression of NCoR, an AR co-repressor, was downregulated during the G1 phase and expressed as mRNA and protein specifically during the S phase. The role of NCoR in repressing androgen-induced expression of AR target genes in S phase was further demonstrated by altering expression of NCoR during the cell cycle through knockdown or induced overexpression. Using two alternative techniques we show that AR binds directly to target DNA in the chromatin only during the G1 phase. These data support the hypothesis that NCoR might control a cell cycle dependent regulation of expression AR target genes in prostate cells.
Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon 1, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon, France.
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DM
Altintas
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Vlaeminck
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D
Angelov
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Dimitrov
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J
Samarut
D000728:Androgens / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000166:cytology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
C410798:AR protein, human; D000728:Androgens; D002843:Chromatin; C539127:NCOR1 protein, human; D056971:Nuclear Receptor Co-Repressor 1; D011944:Receptors, Androgen