RT Journal Article SR Electronic T1 Differential Effects of Aromatase Inhibitors and Antiestrogens on Estrogen Receptor Expression in Breast Cancer Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2167 OP 2171 VO 29 IS 6 A1 MARTIN SMOLLICH A1 MARTIN GÖTTE A1 JEANETT FISCHGRÄBE A1 ISABEL RADKE A1 LUDWIG KIESEL A1 PIA WÜLFING YR 2009 UL http://ar.iiarjournals.org/content/29/6/2167.abstract AB Background: Estrogen receptors (ER) α and β play an important role in breast cancer. Recently, systemic adjuvant endocrine therapy with selective estrogen receptor modulator (SERM) tamoxifen has been challenged by aromatase inhibitors. Compared to antiestrogens, third-generation aromatase inhibitors (anastrozole and letrozole) exhibit an improved efficacy and tolerability. Materials and Methods: Using real-time PCR analysis, 21 breast cancer tissue samples were analysed for a change of the ERα/ERβ ratio during malignant progression. In stimulation experiments, differential effects of SERMs, ER antagonists and aromatase inhibitors have been investigated. Results: Transition from normal breast to grade 1 tumors was characterized by down-regulation of ERβ (relative quantification [RQ]=0.83, p=0.019), while transition from grade 1 to grade 3 tumors was associated with the decrease of ERα expression (RQ=1.14 vs. RQ=0.65, p<0.001). In stimulation assays, tamoxifen and fulvestrant increased ERα expression to RQ=1.51 (p=0.01) and RQ=1.42 (p<0.001), respectively, and left ERβ unchanged. In contrast, aromatase inhibitors up-regulated ERβ to RQ=1.23 (anastrozole, p=0.029) and RQ=1.38 (letrozole, p=0.048). Conclusion: Taken together, data indicate that SERMs/antiestrogens and aromatase inhibitors exhibit opposed effects on the ER expression of breast cancer cells: tamoxifen and fulvestrant up-regulate ERα expression, while aromatase inhibitors increase ERβ expression, which may contribute to the aromatase inhibitors' therapeutic superiority over antiestrogens.