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p73 cooperates with DNA damage agents to induce apoptosis in MCF7 cells in a p53-dependent manner

Oncogene volume 20, pages 4050–4057 (2001)Cite this article

Abstract

p73, a member of the p53 family, can induce apoptosis in cancer cells. Since p53-mediated apoptosis can be augmented by various cancer chemotherapeutic agents, it has been hypothesized that the status of the endogenous p53 gene in cancer cells is a key determinant in the outcome of cancer therapy. To determine whether p73 can sensitize cancer cells to apoptosis by DNA damage agents, several MCF7 adenocarcinoma cell lines that inducibly express p73 or p53 under a tetracycline-regulated promoter were generated. We found that at relevant physiological levels, p73, but not p53, is capable of sensitizing MCF7 cells to apoptosis induced by chemotherapeutic agents. In addition, we found that p73 can cooperate with the DNA damaging agent camptothecin to activate the initiator caspase 2. Furthermore, we found that p73 can cooperate with DNA damaging agents or p53 to induce some p53 target genes and activate their promoters. In contrast, in MCF7E6 cells that ectopically express the human papillomavirus E6 oncogene and are functionally p53-null, the ability of p73 to sensitize cells to apoptosis is abrogated. Taken together, these results suggest that a functional interaction between p53 and p73 in MCF7 cells leads to enhanced induction of apoptosis.

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Acknowledgements

We are grateful to Rhea Markowitz for critical reading of this manuscript. We would like to thank William Kaelin, Jr for providing simian p73 cDNAs. This work is supported in part by Grant RO1 CA81237 from the National Institutes of Health and Grant DAMD 17-97-1-7019 from the DOD Breast Cancer Research Program.

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  1. Institute of Molecular Medicine and Genetics Medical College of Georgia, Augusta, 30912, Georgia, GA, USA

    Jianhui Zhu, Susan Nozell, Jian Wang, Jieyuan Jiang, Wenjing Zhou & Xinbin Chen

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  1. Jianhui Zhu
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  2. Susan Nozell
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Correspondence to Xinbin Chen.

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Zhu, J., Nozell, S., Wang, J. et al. p73 cooperates with DNA damage agents to induce apoptosis in MCF7 cells in a p53-dependent manner. Oncogene 20, 4050–4057 (2001). https://doi.org/10.1038/sj.onc.1204516

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