Epstein-Barr virus gene expression in human breast cancer: protagonist or passenger?
The presence and transcriptional expression of Epstein-Barr virus (EBV)-encoded genes, oestrogen receptor (ER) status and degree of lymphocyte infiltration were evaluated in 15 mastectomy-removed breast cancer samples, mostly of ductal origin. With regard to these parameters, the tumours were heterogeneous. Viral genes, including EBNA1 - a universal EBV marker - and others, selected in part on the basis of expression in other EBV-associated carcinomas and/or presence in an epithelial cell immortalising subfragment p31 of viral DNA, were detected in up to 40% of the breast malignancies. The small viral RNAs, EBERs, were not observed. In culture, p31 EBV DNA, alone among EBV fragments, stimulated the growth of human breast-milk epithelial cells. There was no correlation between viral and ER expression and tumours were heterogeneous with regard to their invasive lymphocytes: of three studied in detail, one contained none, another had (mainly) T-lymphocyte aggregates on the tumour periphery, and a third (BC 12) was infiltrated with both T- and B-lymphocytes. BC 12 differed in several aspects from other malignancies in expressing a transcriptional activator (BZLF1) associated with overcoming virus latency, and failing to express a viral oncogene, BARF1. Arguments are given for EBV as a protagonist cocarcinogen in some breast malignancies.
Xue
S A
SA
Viral Oncology Unit, Division of Medicine, Imperial College Faculty of Medicine at St Mary's, Norfolk Place, London W2 1PG, UK.
Lampert
I A
IA
Haldane
J S
JS
Bridger
J E
JE
Griffin
B E
BE
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology* / Q000821:virology*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology* / Q000821:virology*; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis*; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction; D011960:Receptors, Estrogen / Q000032:analysis* / Q000096:biosynthesis; D013601:T-Lymphocytes
D017931:DNA Primers; D004279:DNA, Viral; D011960:Receptors, Estrogen