Modulation of BAG-1 Expression Alters the Sensitivity of Breast Cancer Cells to Tamoxifen

Cellular Physiology and Biochemistry

关键词: Apoptosis;    Hormonal therapy;    TAM resistance;    BAG-1;    Breast cancer;   

DOI  :  10.1159/000356676

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND