Open AccessLoss of B ‐cell translocation gene 2 expression in estrogen receptor‐positive breast cancer predicts tamoxifen resistance
Author(s) -
Takahashi Maiko,
Hayashida Tetsu,
Okazaki Hiroshi,
Miyao Kazuhiro,
Jinno Hiromitsu,
Kitagawa Yuko
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12410
Subject(s) - tamoxifen , breast cancer , estrogen receptor , medicine , cancer research , gene knockdown , estrogen , cancer , oncology , endocrinology , biology , gene , biochemistry
B‐cell translocation gene 2 ( BTG 2), a gene suppressed in a subset of aggressive breast cancer, is repressed by estrogen. BTG 2 inhibits the expression of HER ligands and promotes AKT activation, which plays an essential role in the tamoxifen resistance of estrogen receptor ( ER )‐positive breast cancer. To determine if BTG 2 expression modifies tamoxifen efficacy, a cohort of 60 patients treated with adjuvant tamoxifen monotherapy was analyzed. We found that increased BTG 2 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). Tamoxifen suppressed the human epidermal growth factor receptor 2 ( HER 2)‐Akt signaling in BTG 2 expressing ER ‐positive breast cancer cells with a correlated increase in sensitivity, whereas BTG 2 knockdown abrogated this sensitivity. Consistent with this observation, tamoxifen significantly suppressed the growth ratio, tumor weight and Ki‐67 expression in BTG 2 expressing breast cancer xenografts in mice. These studies demonstrate that BTG 2 is a significant factor in tamoxifen response, acting through modification of AKT activation in ER ‐positive/ HER 2‐negative breast cancer.