Loss of B-cell translocation gene 2 expression in estrogen receptor-positive breast cancer predicts tamoxifen resistance

Maiko Takahashi, Tetsu Hayashida, Hiroshi Okazaki, Kazuhiro Miyao, Hiromitsu Jinno, Yuko Kitagawa

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

B-cell translocation gene 2 (BTG2), a gene suppressed in a subset of aggressive breast cancer, is repressed by estrogen. BTG2 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 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). Tamoxifen suppressed the human epidermal growth factor receptor 2 (HER2)-Akt signaling in BTG2 expressing ER-positive breast cancer cells with a correlated increase in sensitivity, whereas BTG2 knockdown abrogated this sensitivity. Consistent with this observation, tamoxifen significantly suppressed the growth ratio, tumor weight and Ki-67 expression in BTG2 expressing breast cancer xenografts in mice. These studies demonstrate that BTG2 is a significant factor in tamoxifen response, acting through modification of AKT activation in ER-positive/HER2-negative breast cancer. Tamoxifen treatment effectively inhibits tumor progression with BTG2 expression in mouse xenograft experiment.

Original languageEnglish
Pages (from-to)675-682
Number of pages8
JournalCancer science
Volume105
Issue number6
DOIs
Publication statusPublished - 2014 Jun

Keywords

  • BTG2
  • Breast cancer
  • Drug sensitivity
  • Endocrine therapy
  • Tamoxifen

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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