Loss of B-cell translocation gene 2 expression in estrogen receptor-positive breast cancer predicts tamoxifen resistance.
Bottom Line: To determine if BTG2 expression modifies tamoxifen efficacy, a cohort of 60 patients treated with adjuvant tamoxifen monotherapy was analyzed.We found that increased BTG2 expression showed better clinical survival and was the only independent prognostic factor for disease-free survival (hazard ratio, 0.691; 95% confidence interval, 0.495-0.963; P = 0.029).Consistent with this observation, tamoxifen significantly suppressed the growth ratio, tumor weight and Ki-67 expression in BTG2 expressing breast cancer xenografts in mice.
Affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.Show MeSH
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Mentions: To evaluate the relationship between BTG2 expression and tamoxifen efficacy in vivo, oncogenic H-RASV12 was introduced into the MCF7 cells. This was done because wild-type MCF7 could not constitute a xenograft tumor without additional estrogen management in an immunodeficient mouse; however, estrogen treatment during the experiment would strongly influence tamoxifen efficacy. MCF7-RASV12 maintains characteristics of hormone-sensitive breast cancer and forms tumors in immunodeficient mice without estrogen treatment.20,21 Oncogenic H-RASV12 transformation of MCF7 had no effect on the endogenous level of BTG2 expression (Fig.3a). To assess the cytotoxicity of tamoxifen treatment on BTG2 overexpression, a tetracycline-inducible BTG2 expression model was developed in the MCF7-RASV12 cells. The addition of low concentrations of tetracycline sharply induced BTG2 mRNA expression in both MCF7/tet-BTG2 and MCF7-RASV12/tet-BTG2 cells (Fig.3a). As expected, MCF7-RASV12/tet-BTG2 tumors without BTG2 expression showed less sensitivity to tamoxifen treatment (IC50, 3.0 ± 0.24 μM) than tumors with induced BTG2 expression with statistical significance (IC50, 1.70 ± 0.16 μM; P = 0.043; Fig3b) .
Affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.