Human Cytomegalovirus Infection Enhances NF-κB/p65 Signaling in Inflammatory Breast Cancer Patients

Mohamed El-Shinawi,Amal Younis,Eslam A El-Ghonaimy,Marwa Tantawy,Hossam Taha Mohamed,Mona Mostafa Mohamed,Robert J Schneider,Michael Nevels

doi:10.1371/journal.pone.0055755

Mohamed El-Shinawi, Amal Younis + Show 6 more

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https://doi.org/10.1371/journal.pone.0055755

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Journal: PloS one	Publication Date: Feb 13, 2013
Citations: 110	License type: CC BY 4.0

Affiliation: Ain Shams University, Cairo University, New York University

Abstract

Human Cytomegalovirus (HCMV) is an endemic herpes virus that re-emerges in cancer patients enhancing oncogenic potential. Recent studies have shown that HCMV infection is associated with certain types of cancer morbidity such as glioblastoma. Although HCMV has been detected in breast cancer tissues, its role, if any, in the etiology of specific forms of breast cancer has not been investigated. In the present study we investigated the presence of HCMV infection in inflammatory breast cancer (IBC), a rapidly progressing form of breast cancer characterized by specific molecular signature. We screened for anti-CMV IgG antibodies in peripheral blood of 49 non-IBC invasive ductal carcinoma (IDC) and 28 IBC patients. In addition, we screened for HCMV-DNA in postsurgical cancer and non-cancer breast tissues of non-IBC and IBC patients. We also tested whether HCMV infection can modulate the expression and activation of transcriptional factor NF-κB/p65, a hallmark of IBC. Our results reveal that IBC patients are characterized by a statistically significant increase in HCMV IgG antibody titers compared to non-IBC patients. HCMV-DNA was significantly detected in cancer tissues than in the adjacent non-carcinoma tissues of IBC and IDC, and IBC cancer tissues were significantly more infected with HCMV-DNA compared to IDC. Further, HCMV sequence analysis detected different HCMV strains in IBC patients tissues, but not in the IDC specimens. Moreover, HCMV-infected IBC cancer tissues were found to be enhanced in NF-κB/p65 signaling compared to non-IBC patients. The present results demonstrated a correlation between HCMV infection and IBC. Etiology and causality of HCMV infection with IBC now needs to be rigorously examined.

Highlights

Recent studies suggested that chronic viral infection may have a role in cancer etiology including breast cancer [1]
Ages of non-inflammatory breast cancer (IBC) patients ranged from 29–73 years old (53.3611.3) while ages of IBC patients ranged from 29–65 years old (48.969.9)
Studies have shown that Human Cytomegalovirus (HCMV)-DNA can be detected in colorectal cancer tissues but not in normal tissues of the colon [7], and in carcinoma tissue of malignant glioma [15] and prostate cancer [8]

Summary

Introduction

Recent studies suggested that chronic viral infection may have a role in cancer etiology including breast cancer [1]. DNA tumor viruses such as Epstein–Barr Virus (EBV) and HCMV are of particular interest has been suggested to be involved in certain human cancers given the fact that they are often endemic in the human population [2]. HCMV genes and proteins have been detected in different types of human cancers [6], including colorectal cancer [7], prostate cancer [8], breast cancer [9,10], mucoepidermoid carcinoma of salivary glands [11], glioblastomas [12,13] and medulloblastomas [14]. Studies showed that medulloblastoma and glioma cancer cells possess a suitable environment for HCMV virus to exert its ‘‘oncogenic potential’’ [15,16]. HCMV infection induces the secretion of inflammatory cytokines and growth factors that promote carcinogenesis [6]

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