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Breast Cancer Research and Treatment

, Volume 71, Issue 3, pp 269–280 | Cite as

Normal breast epithelial cells induce p53-dependent apoptosis and p53-independent cell cycle arrest of breast cancer cells

  • Robert-Alain Toillon
  • Valérie Chopin
  • Nathalie Jouy
  • William Fauquette
  • Bénoni Boilly
  • Xuefen Le Bourhis
Article

Abstract

Cancer development depends not only on the nature of cancerous cells themselves, but also on the regulatory effects of various normal cells. The present study was performed to investigate the effect of normal breast epithelial cells (NBEC) on the growth of breast cancer cells under various conditions. We demonstrated that NBEC-conditioned medium (NBEC-CM) inhibited growth of breast cancer cell lines in monolayer culture and three-dimensional collagen gel culture, as well as in soft agar. In MCF-7 and T-47D cells which have a functional p53, NBEC-CM induced apoptosis without modifying cell cycle progression. In MDA-MB-231 and BT-20 cells that have a non-functional p53, NBEC-CM did not induce apoptosis, although a slight G1 blokage was observed in MDA-MB-231 cells. Transient transfections of MCF-7 and T-47D cells demonstrated that NBEC-triggered apoptosis was mediated by endogenous p53. Moreover, pifithrin-α which specifically inhibits the transcriptional activity of p53, completely abolished NBEC-induced apoptosis in both MCF-7 and T-47D cells, indicating that p53 mediated apoptosis via its transcriptional activity. Finally, orthovanadate, a protein tyrosine phosphatase inhibitor, completely inhibited NBEC-triggered apoptosis, indicating that NBEC-triggered apoptosis was regulated by tyrosine phosphatases.

apoptosis breast cancer cell growth normal breast epithelial cells p53 tyrosine phosphatases 

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Robert-Alain Toillon
    • 1
  • Valérie Chopin
    • 1
  • Nathalie Jouy
    • 2
  • William Fauquette
    • 1
  • Bénoni Boilly
    • 1
  • Xuefen Le Bourhis
    • 1
  1. 1.Laboratoire de Biologie du Développement, Equipe facteurs de croissance (UPRES 1033)Université des Sciences et Technologies de LilleVilleneuve d'Ascq CedexFrance
  2. 2.Institut Fédératif de Recherche 22: ‘Biologie et Pathologie des Régulations Cellulaires’Institut de Recherche sur le Cancer de LilleLille CedexFrance

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