title: Epstein-Barr virus (EBV) genome and expression in breast cancer tissue: effect of EBV infection of breast cancer cells on resistance to paclitaxel (Taxol).
abstract: 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.
authors.affiliation: INSERM U716, IUH, IFR Saint-Louis, 27 rue Juliette Dodu, 75010 Paris, France.
authors.forename: Hratch
authors.initials: H
authors.lastname: Arbach
authors.forename: Viktor
authors.initials: V
authors.lastname: Viglasky
authors.forename: Florence
authors.initials: F
authors.lastname: Lefeu
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Guinebretière
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ramirez
authors.forename: Nadège
authors.initials: N
authors.lastname: Bride
authors.forename: Nadia
authors.initials: N
authors.lastname: Boualaga
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauchet
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Peyrat
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Mathieu
authors.forename: Samia
authors.initials: S
authors.lastname: Mourah
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Podgorniak
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Seignerin
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takada
authors.forename: Irène
authors.initials: I
authors.lastname: Joab
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000821:virology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001706:Biopsy; D001940:Breast / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D001943:Breast Neoplasms / Q000473:pathology / Q000821:virology*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D019450:Genes, MDR / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C086495:BARF1 protein, Human herpesvirus 4; D004279:DNA, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; C417029:EBV-encoded nuclear antigen 1; D017239:Paclitaxel