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: Clinical and laboratory evidence supports an essential role for crosstalk between the ER and HER2 signaling pathways in resistance to hormone therapies.13,14,22 As has been shown previously, both estrogen and tamoxifen can activate the HER2 signaling pathway and stimulate tumor growth via non-genomic ER activity.13,23 In addition, suppression of BTG2 strongly induces the activation of HER2 and HER3 phosphorylation, which is reduced by the restoration of BTG2 expression due to neuregulin-1, and epiregulin (EREG) was induced via transcript stabilization on knockdown of BTG2.11 In the immunohistochemical staining of tumors consisted of MCF7-RASV12/tet-BTG2 cells, EREG expression was observed under the condition of loss of BTG2. In contrast, EREG expression was reduced with BTG2 overexpression, which is consistent with the results of a previous study11 (Fig.5a).
Affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.