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1: Science. 2002 Mar 29;295(5564):2465-8.Click here to read Links
Comment in:
Science. 2002 Mar 29;295(5564):2380-1.

Molecular determinants for the tissue specificity of SERMs.

Department of Adult Oncology, Dana-Farber Cancer Institute, 44 Binney Street, and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Selective estrogen receptor modulators (SERMs) mimic estrogen action in certain tissues while opposing it in others. The therapeutic effectiveness of SERMs such as tamoxifen and raloxifene in breast cancer depends on their antiestrogenic activity. In the uterus, however, tamoxifen is estrogenic. Here, we show that both tamoxifen and raloxifene induce the recruitment of corepressors to target gene promoters in mammary cells. In endometrial cells, tamoxifen, but not raloxifene, acts like estrogen by stimulating the recruitment of coactivators to a subset of genes. The estrogen-like activity of tamoxifen in the uterus requires a high level of steroid receptor coactivator 1 (SRC-1) expression. Thus cell type- and promoter-specific differences in coregulator recruitment determine the cellular response to SERMs.

PMID: 11923541 [PubMed - indexed for MEDLINE]