Modulation of BAG-1 expression alters the sensitivity of breast cancer cells to tamoxifen

Hong Liu, Su Lu, Lin Gu, Yongchang Gao, Tong Wang, Jing Zhao, Jianyu Rao, Jun Chen, Xishan Hao, Shou-Ching Tang

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background: BAG-1 (bcl-2 associated athanogene) is a multifunctional protein that protects cells from a wide range of apoptotic stimuli including radiation, hypoxia and chemotherapeutic agents. Overexpression of cytoplasmic BAG-1 has been associated with the increased survival and decreased response to treatment with tamoxifen (TAM) in breast cancer. We attempted to assess the expression of BAG-1 in the human breast cancer cells that are resistant to treatment with 4-OH TAM and effect of altered BAG-1 expression on their sensitivity to 4-OH TAM. Methods: BAG-1 expression was examined in the MCF-7 cells that became resistant to 4-OH TAM. The 4-OH TAM-resistant MCF-7 cells were then transfected with the BAG-1 siRNA and the 4-OH TAM-sensitive MCF-7 cells with the plasmids carrying the human BAG-1 isoform-specific expression constructs respectively to investigate the effect of BAG-1 on the TAM-induced apoptosis. Results: Our results showed that the TAM-resistant MCF-7 (TAMR/MCF-7) cells expressed higher level of BAG-1 than that of the MCF-7 cells. Down-regulation of BAG-1 significantly enhanced the sensitivity of the TAMR/MCF-7 cells to TAM treatment. Additionally, we found that BAG-1 p50 was the only isoform that inhibited the TAM-induced apoptosis in the MCF-7 cells, while the other isoforms had little effect. Conclusion: Our study indicated that up and down regulations of the BAG-1 expression were associated with the decreased and increased sensitivity to 4-OH TAM in the estrogen receptor-positive (ER+) human breast cancer cell line MCF-7 respectively, and distinct isoforms of BAG-1 had different anti-apoptotic ability in breast cancer cells treated with the 4-OH TAM.

Original languageEnglish (US)
Pages (from-to)365-374
Number of pages10
JournalCellular Physiology and Biochemistry
Volume33
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • Apoptosis
  • BAG-1
  • Breast cancer
  • Hormonal therapy
  • TAM resistance

ASJC Scopus subject areas

  • Physiology

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  • Cite this

    Liu, H., Lu, S., Gu, L., Gao, Y., Wang, T., Zhao, J., Rao, J., Chen, J., Hao, X., & Tang, S-C. (2014). Modulation of BAG-1 expression alters the sensitivity of breast cancer cells to tamoxifen. Cellular Physiology and Biochemistry, 33(2), 365-374. https://doi.org/10.1159/000356676