GSE81068

Expression profile of Epstein Barr Virus infected mammary epithelial cells and Breast tumors

Submitted by Gerburg M Wulf (Beth Israel Deaconess Medical Center, USA) on May 03 2016

Platform: microarray – [HT_HG-U133_Plus_PM] Affymetrix HT HG-U133+ PM Array Plate

Pubmed: 27333046

Summary Whether the human tumor virus, Epstein-Barr virus (EBV) promotes breast cancers remains controversial and a potential mechanism has remained elusive. Here we show EBV can infect primary mammary epithelial cells (MECs) that express the attachment receptor, CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype 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, including expression of latent membrane proteins 1 (LMP1) and 2 (LMP2), similar to nasopharyngeal carcinoma (NPC). A human gene expression signature for EBVness was generated based on the RNA expression profile of the EBV infected primary mammary epithelial cells, tumors. This was signature associated with high grade (40 vs 13.5%) estrogen-receptor-negative status (31.8 vs. 10.5%, p53 mutation (37.5 vs 14.5%) and poor survival. In 11/33 (33%) of tumors positive for EBVness EBV-DNA was found in tumor cells by fluorescent in situ hybridization for the viral LMP1 and BXLF2 genes, while only 4/36 (11%) of EBVness-negative tumors tested positive for EBV DNA. An analysis of the TCGA breast cancer data revealed a correlation of EBVness with presence of the APOBEC mutational signatures consistent with past viral infection. We conclude that a contribution of EBV to breast cancer etiology via a ‘hit-and-run’ mechanism is plausible, in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is not required for the maintenance of the malignant phenotype.

16 Samples

ID	Title	Cell Type	Timepoint	Reported Virus	Virus Species	Exclusion Reason
GSM2142062	EBV-MCF-10A	mammary epithelial cell line  [MCF-10A ]	unknown	EBV	Human gammaherpesvirus 4
GSM2142063	GFP-MCF-10A	mammary epithelial cell line  [MCF-10A ]	unknown	GFP	Uninfected
GSM2142064	EBV-MCF-10A-R	mammary epithelial cell line  [MCF-10A ]	unknown	EBV	Human gammaherpesvirus 4	Extra interventions Ras12 over-expression
GSM2142065	GFP-MCF-10A-R	mammary epithelial cell line  [MCF-10A ]	unknown	GFP	Uninfected	Extra interventions Ras12 over-expression
GSM2142066	EBV-HMEC	mammary epithelial cell line	unknown	EBV	Human gammaherpesvirus 4
GSM2142067	GFP-HMEC	mammary epithelial cell line	unknown	GFP	Uninfected
GSM2142068	EBV-HMEC-R	mammary epithelial cell line	unknown	EBV	Human gammaherpesvirus 4	Extra interventions Ras12 over-expression
GSM2142069	GFP-HMEC-R	mammary epithelial cell line	unknown	GFP	Uninfected	Extra interventions Ras12 over-expression
GSM2142070	GFP-tumor 1	breast cancer cell	unknown	GFP	Uninfected	Extra interventions Generated from Ras12 cell line
GSM2142071	GFP-tumor 2	breast cancer cell	unknown	GFP	Uninfected	Extra interventions Generated from Ras12 cell line
GSM2142072	GFP-tumor 3	breast cancer cell	unknown	GFP	Uninfected	Extra interventions Generated from Ras12 cell line
GSM2142073	GFP-tumor 4	breast cancer cell	unknown	GFP	Uninfected	Extra interventions Generated from Ras12 cell line
GSM2142074	EBV-tumor 1	breast cancer cell	unknown	EBV	Human gammaherpesvirus 4	Extra interventions Generated from Ras12 cell line
GSM2142075	EBV-tumor 2	breast cancer cell	unknown	EBV	Human gammaherpesvirus 4	Extra interventions Generated from Ras12 cell line
GSM2142076	EBV-tumor 3	breast cancer cell	unknown	EBV	Human gammaherpesvirus 4	Extra interventions Generated from Ras12 cell line
GSM2142077	EBV-tumor 4	breast cancer cell	unknown	EBV	Human gammaherpesvirus 4	Extra interventions Generated from Ras12 cell line