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P21WAF1/CIP1 is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cells

Oncogene volume 23, pages 21–29 (2004)Cite this article

Abstract

Sodium butyrate (NaB) has been proposed as a potential anticancer agent. However, its mechanism of action is not totally elucidated. Here, we showed that NaB-induced cell cycle arrest and apoptosis were associated with an increase of P21waf1/cip1 in MCF-7 breast cancer cells. This increase was more important in the nuclei, as revealed by immunofluorescence analysis. Transient transfections of MCF-7 cells with p21 deficient for interaction with CDK, but not with p21 deficient for interaction with PCNA (p21PCNA−), abrogated NaB-induced cell cycle arrest. This indicated that cell cycle blockage involved the interaction of P21waf1/cip1 with CDK. However, P21waf1/cip1 was dispensable, since p21 antisense did not modify cell cycle arrest. On the other hand, NaB-induced apoptosis was abolished by p21 antisense or p21PCNA−. In addition, NaB decreased PCNA levels, but increased the association of PCNA with P21waf1/cip1. These results suggested that NaB-induced apoptosis required P21waf1/cip1 and its interaction with PCNA.

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Abbreviations

CDK:

cyclin-dependent kinase

FCS:

fetal calf serum

HDAC:

histone deacetylase

NaB:

sodium butyrate

PCNA:

prolifera-ting cell nuclear antigen

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Acknowledgements

This work was supported by grants from the ‘Ligue Nationale contre le Cancer, Comité du Nord’. We acknowledge the excellent technical assistance of Isabelle LEFEVBRE and Johann ANTOL, and the critical reading of this manuscript by Benoni Boilly and Margaret Howe.

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  1. Equipe facteurs de croissance, Laboratoire de Biologie du Développement (UPRES 1033), IFR 118, Université des Sciences et Technologies de Lille, Villeneuve d', Ascq Cedex, 59655, France

    Valérie Chopin, Robert-Alain Toillon & Xuefen Le Bourhis

  2. IFR 114, IMPRT, ‘Institut de Médecine Prédictive et de Recherche Thérapeutique’, Institut de Recherche sur le Cancer de Lille, Lille Cedex, 59045, France

    Nathalie Jouy

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  1. Valérie Chopin
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Correspondence to Xuefen Le Bourhis.

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Chopin, V., Toillon, RA., Jouy, N. et al. P21WAF1/CIP1 is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cells. Oncogene 23, 21–29 (2004). https://doi.org/10.1038/sj.onc.1207020

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