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|Public on Jul 28, 2006
|Gene Expression Preferentially Regulated by Tamoxifen in Breast Cancer Cells
|Expression profiling by array
|The beneficial effect of the selective
estrogen receptor modulator (SERM) tamoxifen in the treatment and prevention of breast cancer is assumed to be through its ability to antagonize the stimulatory actions of estrogen, although tamoxifen can also have some estrogen-like
agonist effects. Here we report that in addition to these mixed agonist/antagonist actions, tamoxifen can also selectively regulate a unique set of more than 60 genes in estrogen receptor alpha
(ERa)-positive MCF-7 human breast cancer cells which are minimally regulated by estradiol or raloxifene. This gene regulation by tamoxifen is mediated by ERa and is reversed by estradiol or ICI 182,780. We find that the introduction of ERbeta into MCF-7 cells reverses tamoxifen action on approximately 75% of these genes, suggesting that ERbeta is capable of repressing certain actions of tamoxifen. To examine whether these genes might serve as markers of tamoxifen sensitivity and/or the development of resistance, the expression level of these genes was examined in breast tumors of women who had received treatment with tamoxifen. High expression of two of the tamoxifen stimulated genes, YWHAZ/14-3-3z and LOC441453, was found to correlate significantly with disease recurrence following tamoxifen treatment in women with ER-positive tumors, and hence appear to be markers of a poor prognosis.
Our data indicate a new dimension in tamoxifen action, involving gene expression regulation that is tamoxifen-preferential, and identify genes that might serve as markers of tumor responsiveness or resistance to tamoxifen therapy.
Keywords: ligand response in two ER backgrounds
|MCF-7 cells expressing endogenous ERalpha were infected with adenovirus carrying either estrogen receptor beta (AdERb) or no insert (Ad) at multiplicity of infection (moi) of 10. Cells were infected with adenovirus for a period of 48hr before treatment with ligand (vehicle control, 10nM 17beta-estradiol, or 10nM hydroxytamoxifen) for a additional period of 24hr before harvest.
|Chang EC, Frasor J, Katzenellenbogen BS
|Jan 12, 2006
|Last update date
|Aug 10, 2018
|Edmund C Chang
|2225 Colorado Ave
|[HG-U133A] Affymetrix Human Genome U133A Array
|Supplementary data files not provided