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Journal of Virology, January 2006, p. 845-853, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.845-853.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus (EBV) Genome and Expression in Breast Cancer Tissue: Effect of EBV Infection of Breast Cancer Cells on Resistance to Paclitaxel (Taxol)

Hratch Arbach,1 Viktor Viglasky,1,{dagger} Florence Lefeu,1 Jean-Marc Guinebretière,2 Vanessa Ramirez,1 Nadège Bride,1 Nadia Boualaga,1 Thomas Bauchet,1 Jean-Philippe Peyrat,3 Marie-Christine Mathieu,5 Samia Mourah,1 Marie-Pierre Podgorniak,1 Jean-Marie Seignerin,4 Kenzo Takada,6 and Irène Joab1*

INSERM U716, IUH, IFR Saint-Louis, 27 rue Juliette Dodu, 75010 Paris, France,1 Centre René Huguenin, Service de Pathologie, 35 rue Dailly, Saint-Cloud, France,2 Centre Oscar Lambret, laboratoire d'Oncologie Moléculaire Humaine, Lille, France,3 Faculté de Médecine de Grenoble, Laboratoire de Virologie Médicale Moléculaire, Domaine de la Merci, La Tronche, France,4 Institut Gustave Roussy, Villejuif, France,5 Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan6

Received 26 May 2005/ Accepted 4 October 2005

The Epstein-Barr virus (EBV) has been detected in subsets of breast cancers. In order to elaborate on these observations, we quantified by real-time PCR (Q-PCR) the EBV genome in biopsy specimens of breast cancer tissue as well as in tumor cells isolated by microdissection. Our findings show that EBV genomes can be detected by Q-PCR in about half of tumor specimens, usually in low copy numbers. However, we also found that the viral load is highly variable from tumor to tumor. Moreover, EBV genomes are heterogeneously distributed in morphologically identical tumor cells, with some clusters of isolated tumor cells containing relatively high genome numbers while other tumor cells isolated from the same specimen may be negative for EBV DNA. Using reverse transcription-PCR, we detected EBV gene transcripts: EBNA-1 in almost all of the EBV-positive tumors and RNA of the EBV oncoprotein LMP-1 in a smaller subset of the tissues analyzed. Moreover, BARF-1 RNA was detected in half of the cases studied. Furthermore, we observed that in vitro EBV infection of breast carcinoma cells confers resistance to paclitaxel (taxol) and provokes overexpression of a multidrug resistance gene (MDR1). Consequently, even if a small number of breast cancer cells are EBV infected, the impact of EBV infection on the efficiency of anticancer treatment might be of importance.

* Corresponding author. Mailing address: INSERM U716, IUH, IFR Saint-Louis, 27 rue Juliette Dodu, 75010 Paris, France. Phone: 33 (1) 42 49 92 68. Fax: 33 (1) 42 49 48 38. E-mail: Irene.Joab{at}stlouis.inserm.fr.

{dagger} Present address: Institute of Chemistry, Faculty of Sciences, Koöice,Slovak Republic.

Journal of Virology, January 2006, p. 845-853, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.845-853.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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