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Stimulation of the mitogen-activated protein kinase pathway antagonizes TRAIL-induced apoptosis downstream of BID cleavage in human breast cancer MCF-7 cells

Oncogene volume 21, pages 4323–4327 (2002)Cite this article

Abstract

We studied the role of the mitogen-activated protein kinase (MAPK) pathway in the regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in breast tumor MCF-7 cells. We found that addition of a protein kinase C (PKC) activator to MCF-7 cultures prevented TRAIL-induced apoptosis, by inhibiting a step downstream of both caspase-8 activation and BID cleavage. TRAIL-induced translocation of Bax from cytosol to mitochondria, release of cytochrome c from mitochondria and activation of caspase-9 were all inhibited by PKC activation. PKC-mediated prevention of mitochondrial apoptotic events and apoptosis was found to be dependent on the MAPK pathway. Since TRAIL is a ligand of potential use in antineoplastic clinical trials, our findings may provide relevant information in cancer therapy.

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Acknowledgements

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. M Sarker was recipient of a fellowship from Agencia Española de Cooperación Internacional (AECI).

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

    Malabika Sarker, Carmen Ruiz-Ruiz, Gema Robledo & Abelardo López-Rivas

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  1. Malabika Sarker
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  2. Carmen Ruiz-Ruiz
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  3. Gema Robledo
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  4. Abelardo López-Rivas
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Correspondence to Gema Robledo.

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Sarker, M., Ruiz-Ruiz, C., Robledo, G. et al. Stimulation of the mitogen-activated protein kinase pathway antagonizes TRAIL-induced apoptosis downstream of BID cleavage in human breast cancer MCF-7 cells. Oncogene 21, 4323–4327 (2002). https://doi.org/10.1038/sj.onc.1205523

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