No significant correlation between specific antibodies to mouse mammary tumour virus and human cancer

Kovařı́k, Aleš; Hlubinová, K; Prachar, J; Simkovĭc, D; Knotek, J

doi:10.1038/bjc.1989.315

Cited by 15 publications

(9 citation statements)

References 22 publications

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“…Given the similarities across mammalian species, it is not surprising that some women would have developed antibodies against one or more nonviral proteins in the preparations of MMTV that we used. While it is possible that some of the women with reactive sera were exposed to mice, it is more likely that the antibodies we detected were cross-reactive with other cellular antigens, possibly including auto-antibodies (Tax and Manson, 1987;Kovarik et al, 1989). Development of antibodies against nonspecific autoantigens occurs frequently among women with breast cancer (Coronella-Wood and Hersh, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…In 1 : 8 dilutions of sera in enzyme immunoassays, Dion et al found modestly higher reactivity against column-purified p18 from MMTV but not against four other MMTV column-purified proteins or glycoproteins in breast cancer patients compared to controls (Dion et al, 1987). Among 300 Czech subjects (90 healthy controls, 60 with breast cancer, and 150 with other malignancies or serious diseases) whose sera, diluted 1 : 100, were tested by immunoblot heavily loaded with proteins and glycoproteins from the GR/N strain of MMTV, Kovarik et al found frequent reactivity against a 42 kDa cellular contaminant of the virus, but few with reactivity against viral antigens and no differences between cases and controls (Kovarik et al, 1989). All of the previously published studies used only a single strain of MMTV.…”

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confidence: 99%

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Prevalence of serologic reactivity against four strains of mouse mammary tumour virus among US women with breast cancer

2006

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Mouse mammary tumour virus (MMTV) causes breast cancer in mice, and MMTV-specific antibodies develop to high titers among mice infected as adults. Whether MMTV or a related virus infects humans is uncertain, because MMTV DNA sequences have been detected inconsistently and because serologic methods have varied widely. The current study used immunoblot and immunoprecipitation with four strains of MMTV (RIII, FM, C3H, and LA) to detect specific antibodies in 92 sera from US women with breast cancer and in masked dilutions of monoclonal hybridoma and hyperimmunised goat positive-control reagents. In these positive controls, MMTV antibodies of the expected molecular weights were detected at high titer (1 : 100 in the monoclonal reagent, 1 : 10000 in the hyperimmunised goat serum). Nearly 30% of the sera from women with breast cancer had at least one faint band on an immunoblot, but none of these matched the molecular weight of bands revealed by probing the same blot strips with the goat serum. The goat serum readily immunoprecipitated MMTV antigens from all four strains of MMTV, but MMTV antigens were not immunoprecipitated by any of the six breast cancer sera that had four or more nonspecific immunoblot bands. Thus, among women with breast cancer, we found no MMTV-specific antibodies. The upper 95% confidence limit implies that MMTV seroprevalence among breast cancer patients does not exceed 3%.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Prevalence of serologic reactivity against four strains of mouse mammary tumour virus among US women with breast cancer

2006

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“…The Coomassie blue stain, while more sensitive, was known to interfere with immunodetection and so was not evaluated in this study [12,13]. We therefore decided to investigate a number of alternate stains, including the permanent colloidal gold [10,14,15] and colloidal silver stains [16,17], the reversible RevPro stain (Genomics Solution, Chelmsford, MA, USA), and the two fluorescent Sypro Rose and Sypro Ruby stains (Molecular Probes), for their ability to detect proteins at high sensitivity and for their noninterference at the immunodetection level. The result of a comparative study using two loads of a protein lysate (containing tyrosine-phosphorylated proteins) separated by 1-D SDS-PAGE and subsequently blotted onto a PVDF membrane is shown in the first row of Fig.…”

Section: A General Procedures For the Detection Of Tyrosine-phosphorylmentioning

confidence: 99%

A general method for the rapid characterization of tyrosine-phosphorylated proteins by mini two-dimensional gel electrophoresis

Ducret

Desponts²,

Desmarais³

et al. 2000

Electrophoresis

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Our preliminary results are reported in the investigation of the tyrosine phosphorylation cascade triggered by the stimulation of the insulin receptor in the adipocyte cell line 3T3-L1 using a mini two-dimensional gel electrophoresis approach. The minigel format, 8 x 10 cm, was found sufficiently resolving and reproducible to study complex biological samples while considerably increasing throughput and lowering costs compared to larger gel formats. Consequently, we used the minigel format to rapidly screen a large number of samples, of which only the most relevant were then analyzed by optimized, preparative two-dimensional gels. The accurate localization and relative quantification of tyrosine-phosphorylated proteins was performed using a nonradioactive triple labeling method. After transfer onto polyvinylidene difluoride (PVDF) membranes, proteins were stained with Sypro Ruby to verify the separation quality and to localize the general region of interest for immunostaining. The membranes were subsequently blocked with polyvinylpyrrolidone-40 and probed with the relevant antibodies for visualization of the phosphorylated proteins by chemiluminescence. Finally, membranes were stained with colloidal gold to obtain a pattern reminiscent of the silver staining of a polyacrylamide gel. We believe that the presented strategy can be generalized for any gel application in which a protein has to be detected and identified based on its immunoreactivity.

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“…Early studies demonstrated: (1) MMTV-like virus particles in human breast cancer biopsies, cell-lines and breast milk; (2) expression of proteins immunologically cross-reactive with MMTV antigens in human breast cancer biopsies, and (3) serologic evidence of exposure to an MMTV-like agent in women with breast cancer and their healthy daughters, though rarely in control sera (table 1). Whilst provocative, these findings are subject to the criticism that patient numbers were often low and recruited from limited geographical locations, and that investigations of sero-reactivity against individual MMTV proteins did not always confirm disease associations [67,68]. Introduction of molecular biological techniques into the investigation of the human MMTV-like virus essentially halted further studies in this field for 10 years and led to the infective hypothesis for breast cancer being effectively disregarded.…”

Section: The Human Analogue Of Murine Mammary Tumour Virusmentioning

confidence: 99%

“…In 37% of human breast cancer biopsies [51] In human milk [48,52] Produced by T47D human mammary adenocarcinoma cells [53,54] Antigen expression gp52 expressed by the T47D human mammary adenocarcinoma cell line [53,54] 'MMTV tumour associated antigen' found in 14/14 breast carcinomas, but not controls [55] MMTV-gag (p27) reported in 5/6 human milk samples [ MMTV positive sera react mainly with p27 by ELISA [66] p27 & gp 52 seroreactivity predominant in sera from breast cancer patients, reactivity to p30 & p14 seen for both controls and cancer patients by WB [67] no greater reactivity to MMTV gp55, gp34, p28, p18 or p12 in patients than controls by WB/ELISA [68] IEM = Immuno-electron microscopy; RIA = radio-immuno assay; ELISA = enzyme-linked immunosorbent assay; WB = Western blotting.…”

Section: Viral Particlesmentioning

confidence: 99%

A Viral Aetiology for Breast Cancer: Time to Re-Examine the Postulate

Mant

Hodgson²,

Hobday

et al. 2004

Intervirology

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Despite decades of research, no aetiologic factor(s) for human breast cancer has been identified and the search for a causal agent has all but been abandoned during the past thirty years. Over 60 years ago, it was demonstrated that breast tumours in mice are caused by an oncornavirus, murine mammary tumour virus (MMTV). Whilst many at that time postulated a similar virus might be the causative agent of human breast cancer, genetic evidence was difficult to obtain primarily because of the occurrence of endogenous human retrovirus (HER) sequences within the human genome that share extensive regions of nucleotide homology with MMTV. Recently, there has been a resurgence of interest in the possibility that a significant proportion of human breast cancers may be caused by viral infections. Two candidate viruses have been proposed, a human retroviral analogue of MMTV (which differs significantly in sequence and characteristics from HERs) and, the Epstein-Barr virus (γ-herpes virus). These two viruses have been reported to occur in up to 37 and 50% of breast cancer cases, respectively. Here we present the background to the infectious hypothesis for the aetiology of breast cancer and review recent findings.

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No significant correlation between specific antibodies to mouse mammary tumour virus and human cancer

Cited by 15 publications

References 22 publications

Prevalence of serologic reactivity against four strains of mouse mammary tumour virus among US women with breast cancer

Prevalence of serologic reactivity against four strains of mouse mammary tumour virus among US women with breast cancer

A general method for the rapid characterization of tyrosine-phosphorylated proteins by mini two-dimensional gel electrophoresis

A Viral Aetiology for Breast Cancer: Time to Re-Examine the Postulate

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