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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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December 2013 Volume 43 Issue 6

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Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells

  • Authors:
    • Rubí Viedma-Rodriguez
    • Luis Arturo Baiza-Gutman
    • Alejandro García-Carrancá
    • Leticia Moreno-Fierros
    • Fabio Salamanca-Gómez
    • Diego Arenas-Aranda
  • View Affiliations / Copyright

    Affiliations: Unit of Medical Research in Human Genetics, Medical National Center, Century XXI, Mexican Institute of Social Insurance, Mexico City, Mexico, Morphophysiology and Function Unit, Faculty of Higher Studies Iztacala, National Autonomous University of Mexico, Iztacala, Mexico, Cancer Biomedical Research Unit, National Cancer Institute and Biomedical Research Institute, National Autonomous University of Mexico, Mexico City, Mexico, Biomedicine Unit, National Autonomous University of Mexico, Iztacala, Mexico
    Copyright: © Viedma-Rodriguez et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1777-1786
    |
    Published online on: October 4, 2013
       https://doi.org/10.3892/ijo.2013.2127
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Abstract

Apoptosis is controlled by the BCL-2 family of proteins, which can be divided into three different subclasses based on the conservation of BCL-2 homology domains. BIK is a founding member of the BH3-only pro-apoptotic protein family. BIK is predominantly localized in the endoplasmic reticulum (ER) and induces apoptosis through the mitochondrial pathway by mobilizing calcium from the ER to the mitochondria. In this study, we determined that suppression of the death gene Bik promotes resistance to tamoxifen (TAM) in MCF-7 breast cancer cells. We utilized small interfering (siRNA) to specifically knockdown BIK in MCF-7 cells and studied their response to tamoxifen. The levels of cell apoptosis, the potential mitochondrial membrane (∆Ψm), and the activation of total caspases were analyzed. Western blot analysis was used to determine the expression of some BCL-2 family proteins. Flow cytometry studies revealed an increase in apoptosis level in MCF-7 cells and a 2-fold increase in relative BIK messenger RNA (mRNA) expression at a concentration of 6.0 μM of TAM. BIK silencing, with a specific RNAi, blocked TAM-induced apoptosis in 45±6.78% of cells. Moreover, it decreased mitochondrial membrane potential (Ψm) and total caspase activity, and exhibited low expression of pro-apoptotic proteins BAX, BAK, PUMA and a high expression of BCl-2 and MCL-1. The above suggests resistance to TAM, regulating the intrinsic pathway and indicate that BIK comprises an important factor in the process of apoptosis, which may exert an influence the ER pathway, which regulates mitochondrial integrity. Collectively, our results show that BIK is a central component of the programmed cell death of TAM-induced MCF-7 breast cancer cells. The silencing of BIK gene will be useful for future studies to establish the mechanisms of regulation of resistance to TAM.
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Copy and paste a formatted citation
Spandidos Publications style
Viedma-Rodriguez R, Baiza-Gutman LA, García-Carrancá A, Moreno-Fierros L, Salamanca-Gómez F and Arenas-Aranda D: Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells. Int J Oncol 43: 1777-1786, 2013.
APA
Viedma-Rodriguez, R., Baiza-Gutman, L.A., García-Carrancá, A., Moreno-Fierros, L., Salamanca-Gómez, F., & Arenas-Aranda, D. (2013). Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells. International Journal of Oncology, 43, 1777-1786. https://doi.org/10.3892/ijo.2013.2127
MLA
Viedma-Rodriguez, R., Baiza-Gutman, L. A., García-Carrancá, A., Moreno-Fierros, L., Salamanca-Gómez, F., Arenas-Aranda, D."Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells". International Journal of Oncology 43.6 (2013): 1777-1786.
Chicago
Viedma-Rodriguez, R., Baiza-Gutman, L. A., García-Carrancá, A., Moreno-Fierros, L., Salamanca-Gómez, F., Arenas-Aranda, D."Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells". International Journal of Oncology 43, no. 6 (2013): 1777-1786. https://doi.org/10.3892/ijo.2013.2127
Copy and paste a formatted citation
x
Spandidos Publications style
Viedma-Rodriguez R, Baiza-Gutman LA, García-Carrancá A, Moreno-Fierros L, Salamanca-Gómez F and Arenas-Aranda D: Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells. Int J Oncol 43: 1777-1786, 2013.
APA
Viedma-Rodriguez, R., Baiza-Gutman, L.A., García-Carrancá, A., Moreno-Fierros, L., Salamanca-Gómez, F., & Arenas-Aranda, D. (2013). Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells. International Journal of Oncology, 43, 1777-1786. https://doi.org/10.3892/ijo.2013.2127
MLA
Viedma-Rodriguez, R., Baiza-Gutman, L. A., García-Carrancá, A., Moreno-Fierros, L., Salamanca-Gómez, F., Arenas-Aranda, D."Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells". International Journal of Oncology 43.6 (2013): 1777-1786.
Chicago
Viedma-Rodriguez, R., Baiza-Gutman, L. A., García-Carrancá, A., Moreno-Fierros, L., Salamanca-Gómez, F., Arenas-Aranda, D."Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells". International Journal of Oncology 43, no. 6 (2013): 1777-1786. https://doi.org/10.3892/ijo.2013.2127
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