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

13 Citations (Scopus)

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

Fingerprint

Tamoxifen
Breast Neoplasms
MCF-7 Cells
Protein Isoforms
Down-Regulation
Apoptosis
Estrogen Receptors
Small Interfering RNA
Plasmids
Up-Regulation
Radiation
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

Modulation of BAG-1 expression alters the sensitivity of breast cancer cells to tamoxifen. / Liu, Hong; Lu, Su; Gu, Lin; Gao, Yongchang; Wang, Tong; Zhao, Jing; Rao, Jianyu; Chen, Jun; Hao, Xishan; Tang, Shou-Ching.

In: Cellular Physiology and Biochemistry, Vol. 33, No. 2, 02.2014, p. 365-374.

Research output: Contribution to journalArticle

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, vol. 33, no. 2, pp. 365-374. https://doi.org/10.1159/000356676
Liu, Hong ; Lu, Su ; Gu, Lin ; Gao, Yongchang ; Wang, Tong ; Zhao, Jing ; Rao, Jianyu ; Chen, Jun ; Hao, Xishan ; Tang, Shou-Ching. / Modulation of BAG-1 expression alters the sensitivity of breast cancer cells to tamoxifen. In: Cellular Physiology and Biochemistry. 2014 ; Vol. 33, No. 2. pp. 365-374.
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AU - Liu, Hong

AU - Lu, Su

AU - Gu, Lin

AU - Gao, Yongchang

AU - Wang, Tong

AU - Zhao, Jing

AU - Rao, Jianyu

AU - Chen, Jun

AU - Hao, Xishan

AU - Tang, Shou-Ching

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N2 - 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.

AB - 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.

KW - Apoptosis

KW - BAG-1

KW - Breast cancer

KW - Hormonal therapy

KW - TAM resistance

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