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 determine the functional consequence of BTG2 expression in regulating tamoxifen sensitivity, a panel of human breast cancer cell lines was screened for endogenous BTG2 expression. MCF7, an ER-positive breast cancer cell line, showed decreased expression of BTG2 compared with MCF10A, which is an immortalized human mammary epithelial cell line whereas T47D and HCC1500 cell lines, both ER positive, showed increased expression (Fig.2a). Two ER-negative breast cancer cell lines, MDA-MB231 and MDA-MB468, demonstrated a 10-fold reduction in BTG2 expression compared with MCF10A (Fig.2a). An in vitro cytotoxicity assay showed that T47D and HCC1500 expressing the highest levels of endogenous BTG2 had more drug sensitivity than MCF7 (MCF7: IC50, 4.48 ± 0.21 μM; T47D: IC50, 1.31 ± 0.13 μM; HCC1500: IC50, 0.19 ± 0.15 μM). ER-negative MDA-MB468 was not responsive to tamoxifen (IC50 > 25 μM; Fig.2b).
Affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.