Fares, MohamedTaha Mohamed, HossamAbdelaziz Ibrahim, SherifHosney, MohamedI. Rady, MohamedEl-Shinawi, MohamedMostafa Mohamed, Mona2020-03-012020-03-0120191. Omar S, Khaled H, Gaafar R et al. (2003): Breast cancer in Egypt: a review of disease presentation and detection strategies. East Mediterr Health J., 9(3): 448-463. 2. Hance KW, Anderson WF, Devesa SS et al. (2005): Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst., 97(13): 966-975. 3. Schairer C, Brown LM, and Mai PL (2011): Inflammatory breast cancer: high risk of contralateral breast cancer compared to comparably staged noninflammatory breast cancer. Breast Cancer Res Treat, 129(1): 117-124. 4. Dawood S and Cristofanilli M (2011): Inflammatory breast cancer: what progress have we made? Oncology (Williston Park), 25(3): 264-273. 5. Schairer C, Soliman AS, Omar S et al. (2013): Assessment of diagnosis of inflammatory breast cancer cases at two cancer centers in Egypt and Tunisia. Cancer Med., 2(2): 178-184. 6. Giubellino A, Burke TR and Bottaro DP (2008): Grb2 signaling in cell motility and cancer. Expert Opin Ther Targets, 12(8): 1021-1033. 7. Giubellino A, Shi ZD, Jenkins LM et al. (2008): Selectivity and mechanism of action of a growth factor receptor-bound protein 2 SRC homology 2 domain binding antagonist. J Med Chem., 51(23): 7459-7468. 8. Alibek K, Kakpenova A, Mussabekova A et al. (2013): Role of viruses in the development of breast cancer. Infect Agent Cancer, 8(32): 1-6. 9. Landais I and Nelson JA (2013): Functional genomics approaches to understand cytomegalovirus replication, latency and pathogenesis. Curr Opin Virol., 3(4): 408-415. 10.Reyda S, Tenzer S, Navarro P et al. (2014): The tegument protein pp65 of human cytomegalovirus acts as an optional scaffold protein that optimizes protein uploading into viral particles. J Virol., 88(17): 9633-9646. 11.Varnum SM, Streblow DN, Monroe ME et al. (2004): Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. J Virol., 78(20): 10960-10966. 12.Mohamed MM, Al-Raawi D, Sabet SF et al. (2014): Inflammatory breast cancer: New factors contribute to disease etiology: A review. J Adv Res., 5(5): 525-536. 13.Zhang S, Zhou YH, Li L et al. (2010): Monitoring human cytomegalovirus infection with nested PCR: comparison of positive rates in plasma and leukocytes and with quantitative PCR. Virol J., 7: 73. 14.El-Shinawi M, Mohamed HT, Abdel-Fattah HH et al. (2016): Inflammatory and non-inflammatory breast cancer: a potential role for detection of multiple viral DNAs in disease progression. Ann Surg Oncol., 23(2): 494-502. 15.Ijaz M, Shahbaz M, Jiang W et al. (2017): Oncogenic role of Grb2 in breast cancer and Grb2 antagonists as therapeutic drugs. Canc Therapy & Oncol Int J., 3(4): 1-7. 16.Li LY, Li EM, Wu ZY et al. (2014): Overexpression of GRB2 is correlated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma. Int J Clin Exp Pathol., 7(6): 3132-3140. 17.Toki MI, Carvajal-Hausdorf DE, Altan M et al. (2016): EGFR-Grb2 protein colocalization is a prognostic factor unrelated to overall egfr expression or EGFR mutation in lung adenocarcinoma. J Thorac Oncol,, 11(11): 1901-1911. 18.Walter RF, Werner R, Vollbrecht C et al. (2016): ACTB, CDKN1B, GAPDH, GRB2, RHOA and SDCBP were identified as reference genes in neuroendocrine lung cancer via the nCounter Technology. PLoS One, 11(11): 1- 11. 19.Yang L, Wen Y, Lv G et al. (2017): alpha-Lipoic acid inhibits human lung cancer cell proliferation through Grb2- mediated EGFR downregulation. Biochem Biophys Res Commun., 494(1-2): 325-331. 20.Liang C, Xu Y, Ge H et al. (2017): miR-564 inhibits hepatocellular carcinoma cell proliferation and invasion by targeting the GRB2-ERK1/2-AKT axis. Oncotarget, 8(64): 107543-107557. 21.Chen J, Zhang N, Wen J et al. (2017): Silencing TAK1 alters gene expression signatures in bladder cancer cells. Oncol Lett., 13(5): 2975-2981. 22.Ijaz M, Wang F, Shahbaz M et al. (2018): The role of Grb2 in cancer and peptides as Grb2 antagonists. Protein Pept Lett., 24(12): 1084-1095. 23.Kozer N, Barua D, Henderson C et al. (2014): Recruitment of the adaptor protein Grb2 to EGFR Tetramers. Biochemistry, 53(16): 2594-2604. 24.Plummer M, de Martel C, Vignat J et al. (2016): Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health, 4(9): e609-e616. 25.Chen Z, Kolokoltsov AA, Wang J et al. (2012): GRB2 interaction with the ecotropic murine leukemia virus receptor, mCAT-1, controls virus entry and is stimulated by virus binding. Journal of virology, 86(3): 1421-1432. 26.Gannon OM, Antonsson A, Bennett IC et al. (2018): Viral infections and breast cancer - A current perspective. Cancer Lett., 420: 182-189. 27.Baryawno N, Rahbar A, Wolmer-Solberg N et al. (2011): Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target. J Clin Invest., 121(10): 4043-4055. 28.Pasquereau S, Al Moussawi F, Karam W et al. (2017): Cytomegalovirus, macrophages and breast cancer. Open Virol J., 11: 15-27. 29.Touma J, Rahbar A, Davoudi B et al. (2018): Abstract 4222: The prognostic impact of human cytomegalovirus infection in breast cancer. Cancer Research, 78:13 . 30.Gibson W (2008): Structure and formation of the cytomegalovirus virion. Curr Top Microbiol Immunol., 325: 187-204. 31.Cavignac Y, Lieber D, Laib Sampaio K et al. (2015): The cellular proteins Grb2 and DDX3 are increased upon human cytomegalovirus infection and Act in a proviral fashion. PLoS One, 10(6): 1-15. 32.Strunk U, Ramos DG, Saffran HA et al. (2016): Role of herpes simplex virus 1 VP11/12 tyrosine-based binding motifs for Src family kinases, p85, Grb2 and Shc in activation of the phosphoinositide 3-kinase-Akt pathway. Virology, 498: 31-35. 33.Macdonald A, Crowder K, Street A et al. (2004): The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity. J Gen Virol., 85(3): 721-729. 34.Rom S, Pacifici M, Passiatore G et al. (2011): HIV-1 Tat binds to SH3 domains: cellular and viral outcome of Tat/Grb2 interaction. Biochim Biophys Acta, 1813(10): 1836-1844. 35.Rahbar A, Touma J, Costa H et al. (2017): Low expression of estrogen receptor-alpha and progesterone receptor in human breast cancer tissues is associated with high-grade human cytomegalovirus protein expression. Clin Breast Cancer, 17(7): 526-535.https://doi.org/10.12816/EJHM.2019.30754https://t.ly/2dyKGMSA Google ScholarBackground: female mammary carcinoma is the second most common cancer incidence among women and the fifth most common leading cause of cancer death worldwide. Premenopausal young women are more frequently targeted by inflammatory breast cancer (IBC), which is the most lethal form of breast cancer. The human cytomegalovirus (HCMV) has been identified as one of the viral infection with a higher frequency in carcinoma tissues of IBC than in non-IBC. The adaptor protein growth factor receptor-bound protein 2 (Grb2), was found to be upregulated in HCMV-infected cells and play as crucial role in cancer progression. Objective: this study aimed to assess the expression level of Grb2 in carcinoma tissues of IBC and non-IBC with HCMV infection. Patients and Methods: overall, 135 female diagnosed with breast carcinoma were enrolled in this study. Using conventional and real time polymerase chain reaction (PCR), we determined the incidence of HCMV and assessed the expression level of Grb2 mRNA in the breast cancer tissue samples. Results: Grb2 mRNA was significantly upregulated in HCMV+ IBC higher than in HCMV+ non-IBC. According to the molecular subtype, Grb2 mRNA was significantly higher upregulated in breast carcinoma tissues of HCMV+ hormonal positive (HP) than in triple negative (TN) counterparts. Conclusion: HCMV infection is associated with a high expression of Grb2 mRNA in IBC and that HP HCMV+ mammary carcinoma tissues confer upregulated Grb2 mRNA, suggesting a potential role of HCMV infection in enhancing of Grb2 mRNA expression in breast cancer with HP.enGrowth factor receptor-bound protein 2human cytomegalovirusinflammatory breast cancerIncidence of Human Cytomegalovirus in Breast Carcinoma Tissues is Associated with A Higher Expression of Growth Factor Receptor-Bound Protein 2Articlehttps://doi.org/10.12816/EJHM.2019.30754