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At least 505 records · Page 28Linked to original sources
PubMed1991

Growth inhibition of murine mammary carcinoma by monoclonal IgE antibodies specific for the mammary tumor virus.

Two IgE-producing hybridomas were established from spleen cells of Balb/c mice, which had been immunized with mouse mammary tumor virus (MMTV). These IgE monoclonal antibodies (mAbs) reacted specifically with the major envelope glycoprotein (gp36) of MMTV, as established by the immunoblot assay and by passive cutaneous anaphylaxis. The effect of the IgE mAbs (produced by clone A8) on the growth of the MMTV-secreting mammary adenocarcinoma H2712 was investigated in syngeneic C3H/HeJ mice. The mice were inoculated s.c. with either 10(5) (approximately 100 x LD50) or 10(6) (approximately 1000 x LD50) tumor cells and received repeated i.p. injections of 25 micrograms anti-gp36 IgE mAbs at 4-day intervals for 8 weeks. This treatment prevented the development of subcutaneous tumors in 50% of the animals. Similar protection was observed when the tumor cells (10(5)/animal) were injected i.p. 4 days prior to the beginning of the i.p. treatment consisting of injections of 25 micrograms mAbs at 4-day intervals for 6 weeks. However, these mAbs did not protect C3H/HeJ mice against the MMTV-negative MA16/c carcinoma cells. Hence, these results support the view that IgE-mediated cytotoxic mechanisms may play an immunologically specific antitumor surveillance role and that laboratory-induced antitumor IgE mAbs have the potential of specific therapeutic agents for in vivo destruction of tumor cells.

Animals↗
PubMed1996

MMTV-induced mutations in mouse mammary tumors: their potential relevance to human breast cancer.

In mouse mammary tumor virus (MMTV) infected mice, three identifiable stages of mammary tumorigenesis can be biologically defined: preneoplastic hyperplastic nodules, malignant tumor, and distant metastatic lesions (primarily in the lung). MMTV is a biological carcinogen which induces somatic mutations as consequence of its integration into the host cellular genome. Each stage of mammary tumorigenesis appears to result from the clonal outgrowth of cells containing additional integrated proviral MMTV genomes. This phenomenon has provided the basis for an approach to identify genes which, when affected, may contribute to progression through the different stages of mammary tumorigenesis. Eight different genes (Wnt1, Wnt3, Wnt10b, Fgf3, Fgf4, Fgf8, Int3, and Int6) have been shown to be genetically altered in multiple mammary tumors as a consequence of MMTV integration. Although the significance of the human homologs of these genes as targets for somatic mutation during human breast carcinogenesis is only now being explored, it is clear that this work has led to a new appreciation of the complexity of the genetic circuitry that is involved in the control of normal mammary gland growth and development. It seems likely that some of the mutations induced by MMTV, and the signaling pathways in which these target genes take part, will be relevant to the progression from preneoplastic lesions to distant metastasis in human breast cancer.

Animals↗
PubMed1983

Chemical carcinogen-mouse mammary tumor virus interactions in cell transformation.

We have studied the process of mammary cell transformation in vitro using a single cell clone (Clone 18) from a presumptive epithelial cell line, C57MG, derived from a normal mammary gland; a mouse mammary tumor virus (MMTV) host-range variant (RIII)vp4; and the potent initiating carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). After several serial subcultures, cells treated with virus and then with carcinogen exhibited an altered (transformed) morphology, a dramatic increase in anchorage independence, an increase in multinucleation after exposure to cytochalasin B, an enhanced ability to proliferate in low Ca2+ (0.01 mM) medium, and tumorigenicity when inoculated subcutaneously into athymic (nude) mice. Although some of these phenotypic alterations were observed also in cultures treated singly with MMTV or DMBA and in cultures exposed to DMBA before infection with MMTV, enhanced cytochalasin B multinucleation and tumorigenicity were properties observed only in mass cultures of cloned cells first infected with MMTV and then exposed to DMBA. This demonstrates for the first time that exposure of presumptive mammary epithelial cells to MMTV followed by DMBA, but not to either agent alone or to DMBA followed by MMTV, results in malignant transformation of these cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1981

Covert infection of a mouse mammary tumor cell line with Mycoplasma hyorhinis: cosedimentation with mouse mammary tumor virus in sucrose density gradients.

Supernatant fluids from cultures of a mouse mammary tumor (MT) cell line were found to produce a specific cell detachment effect when inoculated into HeLa cells. The cell detachment factor (CDG) responsible for this effect was examined. Repeated attempts to cultivate this CDF in bacteriologic, fungal, and mycoplasma media were unsuccessful. However, using the DNA fluorochrome staining technique and specific immunofluorescent staining procedures, the CDF was identified positively as a noncultivable strain of Mycoplasma hyorhinis. It was also noted that this CDF could be labeled with [3H]uridine in MT cell cultures, concentrated, and banded at a density of 1.18 g/cm3 when centrifuged to equilibrium in a 20 to 60% sucrose gradient. Using a multiple antibiotic treatment regimen, the MT cells were "cured" of the M. hyorhinis contaminant. Re-infection of these cells with an exogenous strain of M. hyorhinis resulted in the same cell detachment effect, and this strain when labeled with [3H]uridine also sedimented at a density of 1.18 g/cm3. The salient feature of these studies is that M. hyorhinis sediments at the same density of mouse mammary tumor virus (MMTV) in sucrose density gradients. This was demonstrated by sucrose density gradient analyses of a purified sample of MMTV, assaying for reverse transcriptase activity, and a [3H]uridine labeled sample of the M. hyorhinis present in the MT cell cultures.

Animals↗
PubMed1981

Possible role of genetic cell variants in the viral induction of mouse mammary tumors.

Out of three attempts to induce neoplasia in normal C57Bl mammary epithelial cells with the mouse mammary tumor virus (MuMTV) only one presented signs of tumorigenicity. Immunofluorescence showed that virus synthesis took place in all three sublines but tumorigenicity as detected by cell aggregation viability (CAV) and transplantation into syngeneic mice failed to occur in two of them. By comparison, cells from a BALB/c spontaneous mammary tumor that do not express MuMTV were 100% tumorigenic, whereas cells from a BALB/cfC3H tumor with a 95% virus-producing cell population had a normal CAV and were tumorigenic only in 60% of the test animals. This lack of correlation suggested that many of the virus-producing cell were not neoplastic and that neoplasia might occur under virus stimulation only if a restricted population of genetic cell variants existed. Accelerated tissue culture passages of virus-free C57Bl and BALB/c normal mammary cells resulted in their spontaneous neoplasia at Passages 23 and 50, respectively; when duplicated cells cryopreserved in early passages were revived and cultivated in the same manner, neoplasia occurred at Passages 27 and 58. The similarity of the passage numbers appears to confirm the existence of genetic cell variants among the normal cell population.

Animals↗
PubMed1997

Possibilities of a viral etiology for human breast cancer. A review.

Previous studies related mouse mammary tumor virus (MMTV) to human breast cancer. However, the presence of human endogenous retroviruses (HERs) confounded these results. We selected a 660-bp sequence of the MMTV env gene with low homology to HER (or any other known gene) and searched for a sequence homologous to it, using the polymerase chain reaction (PCR). The 660-bp sequence was detected in 131 (39%) of 335 unselected breast cancers, in 2 (6.9%) of 29 fibroadenomas, and in 2 (1.65%) of 121 normal breast specimens. The sequence was not present in normal tissues, or in other human cancers or cell lines. Cloning and sequencing of the 660-bp sequence revealed that it is 95-98% homologous to MMTV env gene, but not the known HERs or other viral or human gene. Southern blot hybridization using labeled cloned sequences demonstrated that the 660-bp sequence was present in very low copy number as a 6-8 kb EcoRI fragment only in breast cancer samples and in some of the human breast cancer cell lines that were positive by PCR. Preliminary experiments using reverse transcriptase (RT)-PCR indicated that expression of the 660-bp sequence can be detected in 65% of the positive tumors. We were also able to identify in breast cancer DNA a segment of 1.6 kb comprising LTR and env gene sequences, which are homologous to MMTV, but not to the HERs. The origin of the MMTV-like sequences in tumor DNA could be the result of integrated MMTV-like sequences derived from a human mammary virus.

Animals↗
PubMed1976

Propagation of mouse mammary tumor cell lines and production of mouse mammary tumor virus in a serum-free medium.

Five different mouse mammary tumor cell lines were propagated in a serum free medium. Evaluation of growth characteristics, including logarithmic growth, cell population increase, protein production and days to confluency, showed serum-free medium comparable to serum-containing medium. Mouse mammary tumor virus expression and production, in C3H and GR tumor cell lines, as determined by virus particle counting and RNA dependent DNA polymerase assays, subsequent to dexamethasone stimulation revealed equivalent to higher levels of virus in serum-free medium as compared to serum-containing medium.

Animals↗
PubMed1976

Cell culture factors influencing in vitro expression of mouse mammary tumor virus.

Several cell culture factors were found to influence in vitro expression of mouse mammary tumor virus (MMTV) in the mouse adenocarcinoma cell line Mm5mt/c1. Cells were propagated in a variety of commercially available cell culture media to which dexamethasone (DXM) was added as a stimulator of MMTV production. Culture seeding density, culture medium type, and glucose concentration each influenced MMTV production when expressed on a per cell basis. Maximum cell growth occurred in cultures grown in RPMI-1640 medium containing insulin. Those media which provided good cell growth were not necessarily optimal for virus expression. Addition of insulin did not stimulate MMTV synthesis although dexamethasone alone was stimulatory in all media used; however, maximum MMTV expression was obtained when dexamethasone and insulin were used in concert. Equivalent levels of MMTV-specific cell membrane antigen, MMTV-specific protein, and virus particles were produced at incubation temperatures of 32 degrees, 34 degrees or 37 degrees C; however, higher levels of virus-related RNA-dependent DNA polymerase (RDDP) activity were recovered from cultures incubated at 32 degrees and 34 degrees C than at 37 degrees C. Decreased levels of RDDP were attributed to enzyme thermolability at 37 degrees C incubation.

Animals↗
PubMed1976

Fine structure of a murine mammary carcinoma cell line.

A fine structural study was made of cells from the epithelioid MCF-8/5-2A cell line derived from a MuMTV-free D2 transplantable hyperplastic outgrowth. Electron microscopy shows the cells to be truly epithelial with many cell-to-cell junctions and microvilli. The cells are similar in many respects to normal mouse mammary gland and some of the conventional mammary tumor derived cell lines. This study supports previous observations of the absence of MuMTV in MCF-8 within the limits of morphological detection, and demonstrates the presence of numerous virus particles within, or budding into, cisternae of the endoplasmic reticulum and nuclear envelope. These intracisternal A particles have not been previously described in such abundance in mammary tumor tissue culture cells.

Animals↗
PubMed1995

Superantigenic characteristics of mouse mammary tumor viruses play a critical role in susceptibility to infection in mice.

Mouse mammary tumor viruses (MMTV) are retroviruses that induce mammary carcinomas. An interesting feature of these viruses is the superantigen (SAg) encoded in an open reading frame within the 3' long terminal repeat. The mechanism by which ingestion of milk-borne virus results in infection of the host mammary tissue remains incompletely understood. However, a working model has been proposed in which the interaction between viral SAg, T-cell receptor and MHC class II I-E facilitates viral replication and hence infectivity. In this review we summarize current studies demonstrating the role of SAg stimulation in susceptibility to MMTV infection.

Animals↗
PubMedDate not supplied

Effect of simulated American, Bulgarian, and Japanese human diets and of selenium supplementation on the incidence of virally induced mammary tumors in female mice.

In attempts to simulate the effects of diet on human breast cancer development groups of female C3H mice infected with mammary tumor virus (MMTV-) were maintained on diets formulated to resemble the typical American, Bulgarian, and Japanese human diets. The incidence of mammary tumors was the highest (84%) in group of mice receiving the simulated meat- and fat-rich American diet, which was also low in selenium (Se content: 0.15 ppm). The appearance of mammary tumors was delayed in the mice maintained on the simulated Bulgarian diet, and the final tumor incidence (27%) paralleled the correspondingly lower Bulgarian breast cancer incidence. The simulated Bulgarian diet contained more Se (0.25 ppm), and was lower in fat, meat, and sugar and higher in complex carbohydrates (cereals) than the simulated American diet. In the mice fed the simulated Japanese diet, the appearance of mammary tumors was also delayed, and the tumor incidence was diminished to 47%. In this diet, fish meal was a major source of Se, which is known to have low bioavailability. Additional supplementation of the Japanese-type diet with bioavailable Se (1 ppm) lowered the tumor incidence to 10%. Based on these studies, recommendations are made for breast cancer risk reduction by dietary means.

Aging↗
PubMed1976

Comparative study of the milk fat globule membrane and the mouse mammary tumour virus prepared from the milk of an infected strain of Swiss albino mice.

Milk fat globule membranes and mammary tumour virus particles (d=1.17 g/cm3) have been obtained from the milk of a Swiss albino mice strain. Comparative biochemistry shows that these two structures differ significantly in the phospholipid, polypeptide and glycopolypeptide patterns and enzymatic activities. However, the lipid profile and the morphology of both structures suggest a filiation with the plasma membrane. Density fractions obtained from the crude virus preparation have been thoroughly investigated. The results suggest that most of these fractions represent degraded virus and/or atypical virus assembly.

Animals↗
PubMed1979

Identification, partial purification and biochemical characterization of gamma-glutamyltranspeptidase present as a membrane component in skimmed milk and milk fat-globule membranes, and in mammary-tumour virus from the milk of infected mice.

The enzyme gamma-glutamyltranspeptidase was reproducibly found to be associated with mouse milk particles; it is present in milk fat-globule membranes and mouse mammary-tumour virus of infected Swiss mice, also in particles from the milk of uninfected mice. The enzymatic activities observed range among the highest reported for mammalian tissues. The enzyme was partially purified from mouse mammary-tumour virus, and from milk fat-globule membranes. The molecule requires the presence of detergents to remain soluble, behaves as a high molecular weight component, properties characterizing integral membrane proteins. Kinetics, and the effect of competitors as well as of specific inhibitors show this enzyme to be identical to the well-known kidney gamma-glutamyltranspeptidase ((gamma-glutamyl)-peptide:amino-acid gamma-glutamyltransferase, EC 2.3.2.2). Other oncornaviruses budding from cultured cells originally expressing the enzyme in their plasma membrane also incorporate the enzyme in their structure.

Animals↗