This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Itoh, T. Articles by Chen, S. Search for Related Content PubMed PubMed Citation Articles by Itoh, T. Articles by Chen, S.

---

Cancer Genes and Genomics

Letrozole-, Anastrozole-, and Tamoxifen-Responsive Genes in MCF-7aro Cells: A Microarray Approach

¹ Department of Surgical Research and ² Division of Informational Sciences, Beckman Research Institute of the City of Hope, Duarte, California

Requests for reprints: Shiuan Chen, Department of Surgical Research, Beckman Research Institute of the City of Hope, 1450 East Duarte Road, Duarte, CA 91010. Phone: 626-359-8111, ext. 63454; Fax: 626-301-8972. E-mail: schen{at}coh.org

Antiestrogens and aromatase inhibitors are important drugs in the treatment of estrogen-dependent breast cancer. To investigate the effects of these drugs on gene expression in breast cancer cells, we treated estrogen receptor–positive MCF-7 cells stably transfected with the aromatase gene (known as MCF-7aro cells) with testosterone, 17ß-estradiol, two aromatase inhibitors (letrozole and anastrozole), and an antiestrogen (tamoxifen). We found that testosterone or 17ß-estradiol induced the proliferation of MCF-7aro cells at a rate six times faster than the untreated cells. In addition, the testosterone-induced proliferation of MCF-7aro cells was effectively suppressed by letrozole, anastrozole, or tamoxifen. Microarray analyses on Affymetrix Human Genome U133A GeneChips (Affymetrix, Santa Clara, CA) were carried out using total RNA isolated from the control and treated cells. At the false discovery rate of 0.05 and a minimum fold-change criteria of 1.5, 104 genes were identified that were up-regulated and 109 genes were identified that were down-regulated by both androgen and estrogen. More than 50% of these hormone-regulated genes were counterregulated by all three inhibitors and >90% were counterregulated by at least one of the inhibitors. Comparing the effect of each inhibitor on gene expression, we observed that letrozole and anastrozole are more similar in terms of the genes they affect compared with treatment with tamoxifen. To validate the gene expression profiles identified from microarray analyses, the expression patterns of 13 representative genes were examined by Northern analysis. Finally, the genes identified as statistically significant were classified based on their expression patterns and biological function/pathways. The results of this study provide us with a better understanding of the actions of both aromatase inhibitors and antiestrogens at the molecular level. We believe that the results of this study serve as the first step in identifying unique expression patterns following drug treatment, and that this will ultimately be useful in customizing patient treatment strategies for hormone-dependent breast cancer.

This article has been cited by other articles:

				S. Masri, S. Phung, X. Wang, X. Wu, Y.-C. Yuan, L. Wagman, and S. Chen Genome-Wide Analysis of Aromatase Inhibitor-Resistant, Tamoxifen-Resistant, and Long-Term Estrogen-Deprived Cells Reveals a Role for Estrogen Receptor Cancer Res., June 15, 2008; 68(12): 4910 - 4918. [Abstract] [Full Text] [PDF]

				M. Dolled-Filhart, L. Ryden, M. Cregger, K. Jirstrom, M. Harigopal, R. L. Camp, and D. L. Rimm Classification of breast cancer using genetic algorithms and tissue microarrays. Clin. Cancer Res., November 1, 2006; 12(21): 6459 - 6468. [Abstract] [Full Text] [PDF]