Detection of human mammary tumor virus proteins in human breast cancer cells

Melana, Stella M.; Nepomnaschy, Irene; Hasa, Jennifer; Djougarian, Alina; Djougarian, Anna; Holland, James F.; Pogo, Beatríz G. T.

doi:10.1016/j.jviromet.2009.09.015

Cited by 49 publications

(36 citation statements)

References 29 publications

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“…Additional support for possible involvement of the virus in breast cancer comes from reports claiming that MMTV can infect and spread through a culture of human mammary cells (11,12); the MMTV env protein, through a specific sequence motif, can initiate changes that are consistent with transformation of mammary epithelial cells (13); cells isolated from ascites or pleural effusions of patients with metastatic breast cancer contained MMTV sequences in their DNA, expressed the MMTV Env protein and showed b-retroviral particles by electron microscopy, similar to the mouse virus (14). The same group recently reported detection of HMTV proteins in human breast cancer cells (15).…”

Section: Introductionmentioning

confidence: 96%

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

Feldman

Roniger

Bar-Sinai

et al. 2012

Molecular Cancer Research

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Mouse mammary tumor virus (MMTV) is associated primarily with mammary carcinomas and lymphomas. The signal peptide of the MMTV envelope precursor is uniquely targeted to nucleoli of cells that harbor the virus, where it can function as a nuclear export factor for intron-containing transcripts. Antibodies to this signal peptide, which we refer to as p14, were previously shown to label nucleoli in a subset of human breast cancers. To look for additional cellular functions of p14, different mutants were ectopically expressed in the MCF-7 human breast cancer cell line. This approach identified motifs responsible for its nucleolar targeting, nucleocytoplasmic shuttling, target protein (B23, nucleophosmin) binding, and phosphorylation at serine 18 and 65 both in situ and in vitro. To test the role of these phosphorylation sites, we carried out in vivo tumorigenesis studies in severe combined immunodeficient mice. The findings show that the p14-Ser65Ala mutation is associated with impaired tumorigenicity, whereas the p14-Ser18Ala mutation is associated with enhanced tumorigenicity. Microarray analysis suggests that phosphorylation at serine 18 or at serine 65 is associated with transcriptional regulation of the L5 nucleolar ribosomal protein (a p14 target) and the Erb-B signal transduction pathway. Taken together, these results show that the phosphorylation status of p14 determines whether it functions as a pro-oncogenic or antioncogenic modulator.

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Section: Introductionmentioning

confidence: 96%

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

Feldman

Roniger

Bar-Sinai

et al. 2012

Molecular Cancer Research

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“…[3][4][5][6] HCMV is one of the β-herpesvirus family with infection in 70%-90% of the world's population. It is reactivated periodically after latent infection in the host.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical detection of human cytomegalovirus, Epstein-Barr virus and human papillomavirus in invasive breast carcinoma in Egyptian women: A tissue microarray study

Ahmed

Yussif

2016

JST

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Background and aim: Breast cancer is the commonest malignant tumor and a common cause of cancer death in women all over the world. Some recent studies attributed breast cancer to viral infection. This study aimed to evaluate the expression of HCMV, EBV and HPV in invasive carcinoma of the breast among the Egyptian women by immunohistochemistry and whether there is a relationship between the prognostic factors of breast carcinoma and these viruses. Patients and methods: This retrospective study included 107 selected cases of invasive breast carcinoma. Slides cut from tissue microarray prepared blocks were stained immunohistochemically for HCMV, EBV and HPV antigens. The association of such viruses with the clinicopathological features, tumor recurrence and patient death was evaluated statistically. Result: HCMV, EBV and HPV were present in 43.9%, 10.3% and 24.3% of cases respectively. HCMV was associated significantly with the tumor grade, mitotic count (P = .01), IDC, ER, PR, Her2/neu and molecular subtype (P = .032, .002, .02, .005, .003) respectively. EBV was associated with the tumor size, stage and histological type (P = . 025, .005, .009) respectively. HPV wasn't associated with any of the clinicopathological characteristics. None of these viruses was associated with the tumor recurrence or patient death. Conclusion: HCMV and EBV might be contributing factors for the development and behavioural alteration of breast carcinoma, representing potential tools for the detection of specific therapies for this cancer. Further studies on a larger number of cases using other techniques such as CISH for specific typing of the viruses especially HPV can add more information.

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“…However, recognised risk factors may be absent in 50-80% of patients diagnosed with breast cancer [2], which has created a heightened interest in identifying new risk factors that contribute to the pathogenesis of breast cancer [3]. Recent investigations have linked breast cancer to viral infections, such as Epstein-Barr virus [4], mouse mammary tumour virus, and human papillomavirus (HPV) [5]. The relationship between HPV and other types of cancers, including anogenital, upper aerodigestive tract, and skin cancers, has been well established.…”

Section: Introductionmentioning

confidence: 99%

The role of human papillomavirus infection in breast cancer

et al. 2011

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Breast cancer is the leading female cancer and the third most common cause of cancer deaths worldwide. Many studies have suggested a possible link between breast cancer pathogenesis and viral infection, particularly mouse mammary tumour virus, simian virus 40, Epstein-Barr virus, and human papillomavirus (HPV). A significant number of recent studies have reported that approximately 29% of human breast cancer tissues were positive for high-risk HPV subtypes, especially HPV subtypes 16, 18, or 33. In contrast, several other investigations did not detect any HPV subtypes in either breast cancer tissue or normal breast tissue from patients diagnosed with breast cancer. Given these conflicting data and the established complexity of the association between HPV with other cancers, a definitive relationship between human breast cancer and HPV infection has not been determined. Recent advances in laboratory methodologies aim to overcome the inherent challenges in detecting HPV in breast cancer tissue. There is an urgent need to obtain additional evidence in order to assess the possibility of breast cancer prevention using HPV vaccines.

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Detection of human mammary tumor virus proteins in human breast cancer cells

Cited by 49 publications

References 29 publications

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

The Signal Peptide of Mouse Mammary Tumor Virus-Env: A Phosphoprotein Tumor Modulator

Immunohistochemical detection of human cytomegalovirus, Epstein-Barr virus and human papillomavirus in invasive breast carcinoma in Egyptian women: A tissue microarray study

The role of human papillomavirus infection in breast cancer

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