Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA-RNA hybridization was used to explore whether human neoplasias contain RNA molecules having sequence homologies to those of the RNA tumor viruses known to cause similar diseases in animals. The pattern of specific RNAs found in the human tumors showed a remarkable concordance with the predictions deducible from the animal systems. Thus human breast cancer contains RNA homologous only to that of the murine mammary tumor virus (MMTV). Human leukemias, sarcomas, and lymphomas (including Hodgkin's and Burkitt's) all contain RNA with sequence homology to the murine leukemia virus (RLV) and not to MMTV RNA. Finally, as in the case of the mouse, none of the human tumors examined contain RNA related in sequence to that of the avian myeloblastosis virus (AMV). The RNA detected in all of the human neoplasias was demonstrated to be of high molecular weight (1 times 10(7) daltons) and encapsulated with a reverse transcriptase in particles having densities between 1.16-1.19 g/ml. Further, the RNA of these human tumor particles was related in sequence to the murine viruses that cause the corresponding neoplasias in mice. Thus, 4 features diagnostic for the murine oncogenic viruses are satisfied by the particles found in the human cancers. Finally, it was shown by "recycling" experiments that the DNA from human leukemic cells and from lymphomatous tissue contained particle-related sequences that could not be detected in normal DNA. This finding was further substantiated by studies with identical twins in which it was shown that the leukemic twin contained particle-related sequences that could not be detected in the leukocytes of his identical healthy sibling. These findings are inconsistent with hypotheses that require chromosomal transmission in the germ line of complete copies of the information required to produce malignancy and the associated virus particles.
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PMID:Sequences related to the RNA tumor viruses in the RNA and DNA of human leukemias and lymphomas. 5 26

Rifamycins and distamycins were assayed in vitro for their effects on the activity of a reverse transcriptase derived from the plasma of a patient with breast cancer. The inhibitory effect observed was compared with that of a human placental substance with a molecular weight of approximately 10 000. The latter substance is apparently also capable of affecting reverse transcriptase activity in vitro.
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PMID:In-vitro inhibition of RNA-instructed DNA polymerase. 5 62

The reverse transcriptase in plasma from leukaemic patients perfers the divalent cation Mn++ to Mg++ in the polymerase assay. The reverse is true for the enzyme from plasma of patients with breast cancer. This cation preference is analogous to the cation preference found in B- and C-type RNA-tumour viruses.
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PMID:[Cation preferences of the DNA-polymerases in plasma from patients with leukaemia or breast cancer (author's transl)]. 6 19

We have previously reported [(Ohno, T., Sweet, R.W., Hu, R., DeJak, D. & Spiegelman, S. (1977) Proc. Natl. Acad. Sci. USA 74, 764-768)] on the purification and characterization of the DNA polymerase from human breast cancer particles. Its preference for certain synthetic templates and its ability to use a viral RNA to fashion a faithful DNA transcript identify it as a reverse transcriptase similar to that found in the mouse mammary tumor virus and in the Mason-Pfizer monkey virus (MPMV). We report here that the human breast cancer enzyme crossreacts immunologically with the reverse transcriptase of MPMV. The crossreactivity was shown both by inhibition of enzyme activity and by complex formation between purified enzyme and isolated IgG against MPMV polymerase. No such interactions were observed with other oncornavirus reverse transcriptases of avian, murine, feline, or simian origin. Further, the IgG failed to neutralize the reverse transcriptases from human mesenchymal neoplasias (leukemias and lymphomas) or the activities of normal cellular DNA polymerases (alpha, beta, gamma).
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PMID:Antigenic relatedness of the DNA polymerase of human breast cancer particles to the enzyme of the Mason-Pfizer monkey virus. 6 75

The reverse transcriptase of Mason-Pfizer monkey virus (M-PMV) has been isolated and partially purified by ion exchange chromatography. Sera from rabbits immunized with the partially purified enzyme have been shown by microimmunodiffusion analysis to be immunologically specific for the M-PMV polymerase. The immune serum also specifically inhibits M-PMV polymerase activity and this inhibitory activity has been shown to reside in the IgG fraction of the serum. The application of these reagents to examining virus identity and investigating the possible viral aetiology of human breast cancer is discussed.
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PMID:Production of antiserum to the reverse transcriptase of Mason-Pfizer monkey virus. 7 May 6

Similarities have been observed for some time between oncornavirus-induced malignancies in laboratory animals and leukemias and solid tumors in man. Particles similar to type C oncornaviruses have been detected by electron microscopy both in cells or plasma from leukemia patients and in solid-tumor human malignancies such as Hodgkin's lymphoma, lymphosarcomas, and sarcomas. Likewise, particles resembling type B oncornaviruses in shape and appearance have been found in human breast cancer. In neither case has the infectious nature of the particles been confirmed. However, DNA synthesized in vitro by the enzyme of murine mammary tumor virus was found to hybridize with polysomal RNA obtained from human mammary adenocarcinomas. The presence of RNA complementary to RNA from the Rauscher strain of murine leukemia virus has been observed in other human malignancies unrelated to breast cancer. It has also been found that cells of patients with myelogenous leukemia possess an oncornaviral-type reverse transcriptase that is distinguishable from other cell DNA polymerases and serologically related to the reverse transcriptase of primate oncornaviruses.
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PMID:Human studies following animal models of tumorigenesis by oncornaviruses. 7 Nov 81

All type C retroviruses are lysed by human serum in apparently antibody-independent, complement-mediated reactions. In contrast, we have now determined that the mouse mammary tumor virus (MMTV), a type B retrovirus, is not disrupted by normal human serum. MMTV was lysed, however, when rabbit antibody to whole MMTV was added to the serum. By taking advantage of this dependence of MMTV lysis on specific antibody, a virolytic assay was developed, based on the measurement of reverse transcriptase released from disrupted virions, to search for evidence of antibodies to MMTV in human sera. Significantly greater virolytic activity was detected in the sera of patients with breast cancer than in sera of patients with benign disease (P less than 0.001) or colorectal cancer (P less than 0.001) or in sera from apparently healthy individuals (P less than 0.002). This assay thus appears to be able to detect a unique attribute, possibly the presence of an antibody crossreacting with MMTV, in serum in patient with breast cancer.
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PMID:Virolysis of mouse mammary tumor virus by sera from breast cancer patients. 8 36

Previous studies have identified human breast tumor particles possessing many of the features characteristic of RNA tumor viruses. In addition to the expected size (600 S) and density (1.16 g/ml) these include possession of an outer membrane and an inner one surrounding a "core" containing a DNA polymerase and a large-molecular-weight (70S) RNA possessing detectable homology to the RNAs of the mouse mammary tumor virus (MMTV) and of the Mason-Pfizer monkey virus (MPMV). We report here the purification and characterization of the DNA polymerase from the human breast cancer particles. Its key properties are very similar to those ofthe RNA-dependent DNA nucleotidyltransferase (reverse transcriptase) found in MMTV and MPMV. Thus like these viral enzymes, the purified human breast cancer DNA polymerase exhibits the following three features that together distinguish the known viral reverse transcriptases from normal cellular DNA polymerases: (i) a strong preference for oligo(dT)-poly(rA) over oligo(dT)-poly(dA) as a template for the synthesis of poly(dT); (ii) the acceptance of the highly specific oligo(dG)-poly(rCm) as a template for the formation of poly(dG); (iii) the ability to use a viral RNA (AMV) as a template to fashion a faithful DNA complementary copy; and (iv) its preference for Mg++ over Mn++. In summary, the data described here on the enzyme of the human breast cancer particles add further evidence of similarities to the viral agents associated with the corresponding malignancies in the mouse and monkey models. To date, an enzyme with these properties has not been detected in normal breast tissues or in benign tumors of the breast.
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PMID:Purification and characterization of the DNA polymerase of human breast cancer particles. 26 40

We established a simplified method for the quantitative measurement of pS2 mRNA using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Expression of the pS2 gene, which is transcriptionally induced by estrogen in breast cancer cell line MCF-7 cells, can be repressed by retinoic acid (RA) in unstimulated cells. The suppressive effect of RA on pS2 mRNA was inhibited by cycloheximide.
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PMID:Expression of pS2 gene in human breast cancer cell line MCF-7 is controlled by retinoic acid. 163 3

The primary aims of this study were purification and molecular cloning of a putative retrovirus designated human mammary tumour virus (HMTV). However, our preliminary unpublished data of negative reverse transcriptase (RT) activity in ostensibly 'infected' cells led us to re-examine the evidence for this virus; namely multinucleate giant cell (MNGC) formation and RT activity in cultured blood monocytes from breast cancer patients versus benign breast tumour and normal control subjects. MNGCs from by fusion of monocytes and we estimated the total number of cell fusions which had occurred after 10 days of culture in vitro by counting cells with two, three, four and five or more nuclei (n) and by measuring the density of adherent mononuclear cells for each subject studied. We found no clear-cut difference in MNGC formation between the three subject groups. Moreover, a substantial number of cultures, encompassing the three groups, showed far more MNGCs per 10(5) monocytes than previously reported. Various parametric and nonparametric statistical analyses were performed on the multinucleate cell data and only one parametric test, which utilised the density of monolayers as a co-variate, showed a statistically significant difference at the 5% level between the breast cancer and the normal subject groups. We observed marked subject-to-subject variation in multinucleate cell formation and we suggest that the evidence for a difference between the breast cancer and the normal groups is marginal. Further, MNGC formation by breast cancer monocytes may not be attributed to the presence of a retrovirus since 5'-Azacytidine (AZA), an agent known to stimulate replication of latent retroviruses showed no effect on the MNGC formation. In addition, culture supernatants from the three groups were assayed for RT activity and no test sample gave a significant signal above background. Preliminary transmission electron microscopy analysis failed to identify viral particles in MNGCs.
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PMID:An evaluation of the putative human mammary tumour retrovirus associated with peripheral blood monocytes. 170 75


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