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  • Original Paper
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Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following induction and stabilization of the apoptotic effector Bak

Oncogene volume 19, pages 4108–4116 (2000)Cite this article

Abstract

We demonstrate that treatment of HCW-2 cells, an apoptotic resistant variant of the human HL-60 promyelocytic leukemia cell line with phorbol-12-myristate acetate (PMA), induced differentiation along the monocytic lineage. During this process there was a dramatic increase in the mitochondrial levels of the apoptosis effector, Bak, due to the stabilization of bak mRNA, which was correlated with the sensitization of HCW-2 cells to respond to the apoptotic effect of staurosporine (STS). Treatment of PMA-differentiated, but not undifferentiated, HCW-2 cells induced processing of Bid, substantial efflux of cytochrome c from mitochondria to the cytosol, activation of caspase-3 and apoptosis. The biological significance of the increased mitochondrial Bak in differentiated HCW-2 cells was supported by the finding that transient transfection of a bak cDNA into HCW-2 cells conferred sensitivity to STS-triggered apoptosis, as determined by pro-caspase-3 processing, cytochrome c efflux and DNA fragmentation. Our results suggest that the induction of Bak, upon monocytic differentiation, may be a critical event that regulates the apoptotic sensitivity of differentiated HCW-2 cells.

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Acknowledgements

This work was supported by a National Science Foundation grant MCB-9630362 (to JH Wyche and EA Hendrickson). TA Bremner was supported as a Howard Hughes Visiting Professor by a grant from the Howard Hughes Medical Institute to Brown University (5-29251).

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Authors and Affiliations

  1. Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 69 Brown Street, Providence, 02912, Rhode Island, RI, USA

    Devasis Chatterjee, Panayotis Pantazis, Gang Li, Theodore A Bremner, Eric A Hendrickson & James H Wyche

  2. Department of Biology, Howard University, Washington, 20059, DC, USA

    Theodore A Bremner

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Chatterjee, D., Pantazis, P., Li, G. et al. Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following induction and stabilization of the apoptotic effector Bak. Oncogene 19, 4108–4116 (2000). https://doi.org/10.1038/sj.onc.1203757

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