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The differential sensitivity of Bc1-2-overexpressing human breast tumor cells to TRAIL or doxorubicin-induced apoptosis is dependent on Bc1-2 protein levels

Oncogene volume 20, pages 7128–7133 (2001)Cite this article

Abstract

Bc1-2 protein is a potent anti-apoptotic protein that inhibits a mitochondria-operated pathway of apoptosis in many cells. DNA damaging agents and death receptor ligands can activate this mitochondrial apoptotic mechanism. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been suggested to escape from the inhibitory action of Bc1-2 protein. We show that in human breast tumor MCF-7 cells, TRAIL induced a mitochondrial pathway of apoptosis that involved cytochrome c release from mitochondria and activation of caspase 9. The DNA damaging drug doxorubicin also activated this mitochondria-regulated mechanism of apoptosis, which was inhibited in Bc1-2-overexpressing cells. We also demonstrate that in MCF-7 cells Bc1-2 might confer resistance to TRAIL-induced apoptosis, depending on the expression levels of the anti-apoptotic protein. These results indicate that enhanced expression of Bc1-2 in tumor cells can render these cells less sensitive not only to chemotherapeutic drugs but also to TRAIL.

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Acknowledgements

pcDNA3-bc1-2 plasmid was kindly provided by Dr Jacint Boix (University of Lleida, Lleida, Spain). This work was supported by grants from the Comisión Interministerial de Ciencia y Tecnología (1FD97-0514-C02-01 and SAF2000-0118-C03-01) to A López-Rivas. C Ruiz de Almodóvar and C Muñoz-Pinedo were recipients of fellowships from Fondo de Investigación Sanitaria (FIS, Exp. 00/9319) and Formación de Personal Investigador (FPI), respectively.

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  1. Instituto de Parasitología y Biomedicina CSIC, calle Ventanilla 11, Granada, 18001, Spain

    Carmen Ruiz de Almodóvar, Carmen Ruiz-Ruiz, Cristina Muñoz-Pinedo, Gema Robledo & Abelardo López-Rivas

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  1. Carmen Ruiz de Almodóvar
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Correspondence to Abelardo López-Rivas.

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de Almodóvar, C., Ruiz-Ruiz, C., Muñoz-Pinedo, C. et al. The differential sensitivity of Bc1-2-overexpressing human breast tumor cells to TRAIL or doxorubicin-induced apoptosis is dependent on Bc1-2 protein levels. Oncogene 20, 7128–7133 (2001). https://doi.org/10.1038/sj.onc.1204887

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