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Progesterone prevents radiation-induced apoptosis in breast cancer cells

Oncogene volume 23, pages 4603–4613 (2004)Cite this article

Abstract

Sex steroid hormones play an essential role in the control of homeostasis in the mammary gland. Although the involvement of progesterone in cellular proliferation and differentiation is well established, its exact role in the control of cell death still remains unclear. As dysregulation of the apoptotic process plays an important role in the pathogenesis of breast cancer, we investigated the regulation of apoptosis by progesterone in various breast cancer cell lines. Our results show that progesterone treatment protects against radiation-induced apoptosis. This prevention appears to be mediated by the progesterone receptor and is unrelated to p53 status. There is also no correlation with the intrinsic hormonal effect on cell proliferation, as the presence of cells in a particular phase of the cell cycle. Surprisingly, progesterone partly allows bypassing of the irradiation-induced growth arrest in G2/M in PgR+ cells, leading to an increase in cell proliferation after irradiation. One consequence of this effect is a higher rate of chromosome damage in these proliferating progesterone-treated cells compared to what is observed in untreated irradiated cells. We propose that progesterone, by inhibiting apoptosis and promoting the proliferation of cells with DNA damage, potentially facilitates the emergence of genetic mutations that may play a role in malignant transformation.

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Acknowledgements

This work was supported by grants from Electricité de France (EDF).

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Authors and Affiliations

  1. Département de Radiobiologie et Radiopathologie, Laboratoire de Cancérologie Expérimentale, Commissariat à l'Energie Atomique, Fontenay-aux-Roses cedex, 92265, France

    Guillaume Vares, Katherine Ory, Bruno Lectard, Céline Levalois, Sandrine Altmeyer-Morel, Sylvie Chevillard & Jérôme Lebeau

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  1. Guillaume Vares
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  2. Katherine Ory
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Correspondence to Jérôme Lebeau.

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Vares, G., Ory, K., Lectard, B. et al. Progesterone prevents radiation-induced apoptosis in breast cancer cells. Oncogene 23, 4603–4613 (2004). https://doi.org/10.1038/sj.onc.1207601

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