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Apoptosis in the absence of caspase 3

Oncogene volume 20, pages 6570–6578 (2001)Cite this article

Abstract

MCF-7 human breast cancer cells do not express caspase 3, thought by some to be a critical component of the apoptosis cascade. Nonetheless, both mock- and bcl-2-transfected MCF-7 cells undergo apoptosis after treatment with a variety of stimuli, including the DNA-cleaving antimitotic agent, neocarzinostatin (NCS). Transfection with bcl-2 shifts the concentration-response curve to NCS but does not change the phenomenology of apoptosis when it occurs. In both cases, NCS treatment results in condensation and fragmentation of MCF-7 cell nuclei and release of cytochrome c from the mitochondria to the cytosol. This apoptosis is accompanied by decreased levels of Bcl-2 and increased levels of Bax. Using a series of caspase inhibitors with overlapping specificities, enzyme-specific chromogenic substrates, and an antibody specific for activated caspase 7, we have determined that apoptosis in MCF-7 cells proceeds via sequential activation of caspases 9, 7 and 6. P21 is detected only after activation of caspase 7, and P53 is neither expressed at baseline nor up-regulated with apoptosis induction. This pathway bypasses the need for activated caspase 3 in these cells.

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Acknowledgements

This work was supported by a grant from the National Institutes of Health (R01-CA74289) and the Carol Ann Craumer Endowment Fund of Children's Hospital of Pittsburgh.

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Authors and Affiliations

  1. Pediatric Center for Neuroscience, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Ye Liang, Chaohua Yan & Nina F Schor

  2. Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Nina F Schor

  3. Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Nina F Schor

  4. Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Nina F Schor

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  1. Ye Liang
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  2. Chaohua Yan
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  3. Nina F Schor
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Correspondence to Nina F Schor.

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Liang, Y., Yan, C. & Schor, N. Apoptosis in the absence of caspase 3. Oncogene 20, 6570–6578 (2001). https://doi.org/10.1038/sj.onc.1204815

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