期刊
ENDOCRINOLOGY
卷 151, 期 4, 页码 1662-1667出版社
ENDOCRINE SOC
DOI: 10.1210/en.2009-1028
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资金
- National Institutes of Health [CA69056, CA102360]
- NATIONAL CANCER INSTITUTE [R01CA102360, R01CA069056] Funding Source: NIH RePORTER
3,3'-Diindolylmethane (DIM) is a natural compound found in cruciferous vegetables that has antiproliferative and estrogenic activity. However, it is not clear whether the estrogenic effects are mediated through estrogen receptor (ER)alpha, ER beta, or both ER subtypes. We investigated whether DIM has ER subtype selectivity on gene transcription. DIM stimulated ER beta but not ER alpha activation of an estrogen response element upstream of the luciferase reporter gene. DIM also selectively activated multiple endogenous genes through ER beta. DIM did not bind to ER beta, indicating that it activates genes by a ligand-independent mechanism. DIM causes ER beta to bind regulatory elements and recruit the steroid receptor coactivator (SRC)-2 coactivator, which leads to the activation of ER target genes. Silencing of SRC-2 inhibited the activation of ER target genes, demonstrating that SRC-2 is required for transcriptional activation by DIM. Our results demonstrate that DIM is a new class of ER beta-selective compounds, because it does not bind to ER beta, but instead it selectively recruits ER beta and coactivators to target genes. (Endocrinology 151: 1662-1667, 2010)
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