Epstein-Barr virus (EBV) genome and expression in breast cancer tissue: effect of EBV infection of breast cancer cells on resistance to paclitaxel (Taxol).
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.
Arbach
Hratch
H
INSERM U716, IUH, IFR Saint-Louis, 27 rue Juliette Dodu, 75010 Paris, France.
Viglasky
Viktor
V
Lefeu
Florence
F
Guinebretière
Jean-Marc
JM
Ramirez
Vanessa
V
Bride
Nadège
N
Boualaga
Nadia
N
Bauchet
Thomas
T
Peyrat
Jean-Philippe
JP
Mathieu
Marie-Christine
MC
Mourah
Samia
S
Podgorniak
Marie-Pierre
MP
Seignerin
Jean-Marie
JM
Takada
Kenzo
K
Joab
Irène
I
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
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