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Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation()

Whether 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...

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Autores principales: Hu, Hai, Luo, Man-Li, Desmedt, Christine, Nabavi, Sheida, Yadegarynia, Sina, Hong, Alex, Konstantinopoulos, Panagiotis A., Gabrielson, Edward, Hines-Boykin, Rebecca, Pihan, German, Yuan, Xin, Sotirious, Christos, Dittmer, Dirk P., Fingeroth, Joyce D., Wulf, Gerburg M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972522/
https://www.ncbi.nlm.nih.gov/pubmed/27333046
http://dx.doi.org/10.1016/j.ebiom.2016.05.025
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author Hu, Hai
Luo, Man-Li
Desmedt, Christine
Nabavi, Sheida
Yadegarynia, Sina
Hong, Alex
Konstantinopoulos, Panagiotis A.
Gabrielson, Edward
Hines-Boykin, Rebecca
Pihan, German
Yuan, Xin
Sotirious, Christos
Dittmer, Dirk P.
Fingeroth, Joyce D.
Wulf, Gerburg M.
author_facet Hu, Hai
Luo, Man-Li
Desmedt, Christine
Nabavi, Sheida
Yadegarynia, Sina
Hong, Alex
Konstantinopoulos, Panagiotis A.
Gabrielson, Edward
Hines-Boykin, Rebecca
Pihan, German
Yuan, Xin
Sotirious, Christos
Dittmer, Dirk P.
Fingeroth, Joyce D.
Wulf, Gerburg M.
author_sort Hu, Hai
collection PubMed
description Whether 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.
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spelling pubmed-49725222016-08-10 Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation() Hu, Hai Luo, Man-Li Desmedt, Christine Nabavi, Sheida Yadegarynia, Sina Hong, Alex Konstantinopoulos, Panagiotis A. Gabrielson, Edward Hines-Boykin, Rebecca Pihan, German Yuan, Xin Sotirious, Christos Dittmer, Dirk P. Fingeroth, Joyce D. Wulf, Gerburg M. EBioMedicine Research Paper Whether 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. Elsevier 2016-05-21 /pmc/articles/PMC4972522/ /pubmed/27333046 http://dx.doi.org/10.1016/j.ebiom.2016.05.025 Text en © 2016 Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Hu, Hai
Luo, Man-Li
Desmedt, Christine
Nabavi, Sheida
Yadegarynia, Sina
Hong, Alex
Konstantinopoulos, Panagiotis A.
Gabrielson, Edward
Hines-Boykin, Rebecca
Pihan, German
Yuan, Xin
Sotirious, Christos
Dittmer, Dirk P.
Fingeroth, Joyce D.
Wulf, Gerburg M.
Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation()
title Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation()
title_full Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation()
title_fullStr Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation()
title_full_unstemmed Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation()
title_short Epstein–Barr Virus Infection of Mammary Epithelial Cells Promotes Malignant Transformation()
title_sort epstein–barr virus infection of mammary epithelial cells promotes malignant transformation()
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972522/
https://www.ncbi.nlm.nih.gov/pubmed/27333046
http://dx.doi.org/10.1016/j.ebiom.2016.05.025
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