MMTV-like env gene sequences in human breast cancer

Wang, Y.; Pelisson, Isabelle; Melana, Stella M.; Go, Vera S; Holland, James F.; Pogo, Beatríz G. T.

doi:10.1007/s007050170201

Cited by 91 publications

(158 citation statements)

References 17 publications

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“…Although this is the first report demonstrating evidence for betaretrovirus infection in patients with PBC, our findings are concordant with other investigators who have provided immunochemical, serologic, molecular hybridization and electron microscopy evidence of a human betaretrovirus infection in patients with breast cancer and healthy subjects (13,18,(25)(26)(27)(28). Full-length proviral betaretroviral sequences have been cloned from one PBC patients' peri-portal lymph node and two human breast cancer samples and fluorescent in situ hybridization studies have shown betaretrovirus integration in human chromosomes from metastatic breast cancer cells (ref.…”

Section: Discussionsupporting

confidence: 92%

“…These studies do not directly address a causal relationship between microbe and disease but they support the numerous reports documenting the presence of a betaretrovirus infection in humans (13,18,(25)(26)(27)(28). In this regard, we have devised a coculture model that can be used to test Koch's postulates in vitro by using either pure isolates or transfected DNA of the human betaretrovirus.…”

Section: Discussionmentioning

confidence: 73%

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Does a betaretrovirus infection trigger primary biliary cirrhosis?

Shen

Guo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

217

246

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Patients with primary biliary cirrhosis develop progressive ductopenia associated with the production of antimitochondrial antibodies that react with a protein aberrantly expressed on biliary epithelial cells and peri-hepatic lymph nodes. Although no specific microbe has been identified, it is thought that an infectious agent triggers this autoimmune liver disease in genetically predisposed individuals. Previous serologic studies have provided evidence to suggest a viral association with primary biliary cirrhosis. Here we describe the identification of viral particles in biliary epithelium by electron microscopy and the cloning of exogenous retroviral nucleotide sequences from patients with primary biliary cirrhosis. The putative agent is referred to as the human betaretrovirus because it shares close homology with the murine mammary tumor virus and a human retrovirus cloned from breast cancer tissue. In vivo, we have found that the majority of patients with primary biliary cirrhosis have both RT-PCR and immunohistochemistry evidence of human betaretrovirus infection in lymph nodes. Moreover, the viral proteins colocalize to cells demonstrating aberrant autoantigen expression. In vitro, we have found that lymph node homogenates from patients with primary biliary cirrhosis can induce autoantigen expression in normal biliary epithelial cells in coculture. Normal biliary epithelial cells also develop the phenotypic manifestation of primary biliary cirrhosis when cocultivated in serial passage with supernatants containing the human betaretrovirus or the murine mammary tumor virus, providing a model to test Koch's postulates in vitro.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 73%

Does a betaretrovirus infection trigger primary biliary cirrhosis?

Shen

Guo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

217

246

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“…During the 1970s, MMTV was suggested to play a role in the etiology of human breast cancer when claims were first made that MMTV antigens were involved in this disease (3). A new wave of interest in this issue started in the mid-1990s when MMTV DNA sequences were first identified, using PCR technology, in 38% of human breast cancer samples, but not in healthy tissue (4). Despite the lack of incontrovertible evidence for a causal relationship between MMTV and breast cancer and doubts whether MMTV is a tumor virus or just a "rumor" virus in the context of this disease (ref.…”

Section: Introductionmentioning

confidence: 99%

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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“…MMTV env gene plasmid and MCF-7 and MB-MDA-231 cell lines were used as a positive control, as described in previous studies. 1,2,11,17 The viral sequence was first amplified by regular PCR; then, PCR products were hybridized with an internal probe by PCR Southern hybridization; finally, real-time PCR was performed. We were unable to detect the viral sequence in the cell lines or in the breast tumor tissues despite robust amplification from the plasmid control.…”

mentioning

confidence: 99%

Mouse mammary tumor‐like env gene as a molecular marker for breast cancer?

Zangen

Harden

Cohen

et al. 2002

Intl Journal of Cancer

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Dear Sir,The involvement of the mouse mammary tumor virus (MMTV) in breast cancer has long been postulated but never proven. Two studies have detected the sequence of the MMTV env gene in more than one-third of breast tumor tissues. 1,2 The present study was designed to investigate whether this viral sequence could serve as a molecular marker for the detection of breast cancer. We amplified the viral sequence in 2 cell lines and 18 breast tumor samples, using PCR, PCR Southern hybridization and real-time PCR. Surprisingly, we could not detect the viral sequence in any of these samples despite amplification in positive controls. Our study calls into question the role of MMTV in human breast cancer tumorigenesis.The involvement of retroviruses in human cancer was established long ago, e.g., HPV in cervical and oropharyngeal tumors. 3,4 The participation of a virus similar to MMTV in human breast cancer has long been postulated but never demonstrated. Several lines of evidence suggested the involvement of MMTV-like retroviruses in human breast cancer. Previously, it was shown that MMTV is an agent associated with a high incidence of breast cancer in mice. 5 Detectable MMTV env gene-related antigenic reactivity was found in tissue sections of breast cancer, 6 -10 breast cancer cell lines, 11 serum, 12,13 pleural effusion 14 and lymph nodes. 15 Moreover, sequence homology to MMTV has been found in human DNA. 1,2,16 -21 Two studies detected the env gene of MMTV in 37-38.5% of breast tumor tissues but only in 0 -2% of normal tissues. 1,2 According to these studies, this viral sequence was highly specific to breast tumor tissues and was not detected in other tumor tissues.The present study was designed to examine whether the env gene of MMTV could be used as a molecular marker for the detection of breast cancer. We planned to evaluate, by real-time PCR, a panel of normal tissues, tumor breast tissues and blood samples from 40 breast cancer patients. MMTV env gene plasmid and MCF-7 and MB-MDA-231 cell lines were used as a positive control, as described in previous studies. 1,2,11,17 The viral sequence was first amplified by regular PCR; then, PCR products were hybridized with an internal probe by PCR Southern hybridization; finally, real-time PCR was performed. We were unable to detect the viral sequence in the cell lines or in the breast tumor tissues despite robust amplification from the plasmid control. MATERIAL AND METHODS Cell lines and tumor tissuesThe MCF-7 and MB-MDA-231 cell lines were purchased from the ATCC (Manassas, VA) and grown in RPMI medium with FBS 10%, penicillin and streptomycin 1%.Eighteen invasive ductal carcinomas of the breast from 17 patients were collected at the

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MMTV-like env gene sequences in human breast cancer

Cited by 91 publications

References 17 publications

Does a betaretrovirus infection trigger primary biliary cirrhosis?

Does a betaretrovirus infection trigger primary biliary cirrhosis?

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

Mouse mammary tumor‐like env gene as a molecular marker for breast cancer?

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