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Model Organisms

Tamoxifen Functions As a Molecular Agonist Inducing Cell Cycle-Associated Genes in Breast Cancer Cells^1,2

¹ Department of Carcinogenesis, UT M.D. Anderson Cancer Center, Smithville, TX;
² Laboratory of Molecular Carcinogenesis and ³ Biostatistics Branch, National Institute for Environmental Health Sciences, Research Triangle Park, NC

Requests for reprints: Cheryl Lyn Walker, Department of Carcinogenesis, UT M.D. Anderson Cancer Center, Science Park-Research Division, P. O. Box 389, Smithville, TX 78957. Phone: (512) 237-9550; Fax: (512) 237-2475. E-mail: cwalker{at}odin.mdacc.tmc.edu

Tamoxifen is a widely used breast cancer therapeutic and preventative agent. Although functioning as an estrogen antagonist at the cellular level, transcriptional profiling revealed that at the molecular level, tamoxifen functions largely as an agonist, virtually recapitulating the gene expression profile induced in breast cancer cells by estrogen. Remarkably, tamoxifen induces transcription factors and genes involved in promoting cell cycle progression including fos, myc, myb, cdc25a, cyclins E and A2, and stk15 with kinetics that paralleled that of cells cycling in response to estrogen, even though tamoxifen-treated cells are not transiting through the cell cycle. Induction of cell cycle-associated genes was specific for tamoxifen, and did not occur with raloxifene. However, cyclin D1 was a key estrogen-induced gene not expressed in response to tamoxifen or raloxifene but constitutively expressed in tamoxifen-resistant cells.

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