Epstein-Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation
Access full-text PDFOpen Access
Check access options
Check access options
UMass Chan AffiliationsDepartment of Medicine, Division of Infectious Diseases and Immunology
Document TypeJournal Article
MetadataShow full item record
AbstractWhether the human tumor virus, Epstein-Barr Virus (EBV), promotes breast cancer remains controversial and a potential mechanism has remained elusive. Here we show that EBV can infect primary mammary epithelial cells (MECs) that express the receptor CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype, activates MET signaling and enforces a differentiation block. When MECs were implanted as xenografts, EBV infection cooperated with activated Ras and accelerated the formation of breast cancer. Infection in EBV-related tumors was of a latency type II pattern, similar to nasopharyngeal carcinoma (NPC). A human gene expression signature for MECs infected with EBV, termed EBVness, was associated with high grade, estrogen-receptor-negative status, p53 mutation and poor survival. In 11/33 EBVness-positive tumors, EBV-DNA was detected by fluorescent in situ hybridization for the viral LMP1 and BXLF2 genes. In an analysis of the TCGA breast cancer data EBVness correlated with the presence of the APOBEC mutational signature. We conclude that a contribution of EBV to breast cancer etiology is plausible, through a mechanism in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is no longer required once malignant transformation has occurred.
SourceEBioMedicine. 2016 Jul;9:148-60. doi: 10.1016/j.ebiom.2016.05.025. Epub 2016 May 21. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/39992
Full author list omitted for brevity. For full list of authors see article.
Related ResourcesLink to Article in PubMed
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-nd/4.0/