Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracisternal A particles (IAPs) are retrovirus-like structures consistently observable in a variety of mouse tumor cells such as myeloma and hybridoma and in early embryonic cells derived from rodents but nothing is known of their infectivity. Mouse IAPs contain a gag-like protein, a reverse transcriptase and a polyadenylated RNA molecule (IAP RNA). DNA sequences complementary to IAP RNA (IAP genome) are interspersedly present in rodent such as mice, rats, Chinese hamsters and Syrian hamsters at several hundred to a thousand copies per haploid genome. Molecularly cloned IAP genomes from two species Mus and Syrian hamster were 6 to 8 kb in length with LTRs of about 0.4 kb long. The nucleotide sequence of the Syrian hamster IAP genome, H18, predicted a typical LTR-gag-prt-pol-env-LTR structure, although many stop codons were present in the region corresponding to env. The comparison of the deduced amino acid sequences of the pol region showed IAP (type A), mouse mammary tumor virus (MMTV) (type B), and squirrel monkey retrovirus (SMRV) (type D) genomes to be closely related. By using a DNA fragment encoding the pol region of the Syrian hamster IAP genome, human endogenous retroviruses termed HERV-K, were cloned from a fetal human liver gene library. Typical HERV-K genome was 9.5 kb in length having LTRs of about 1.0 kb. The HERV-K provirus could encode gag (666 codons), prt (334 codons), pol (937 codons), and env (618 codons) genes. HERV-K was shown to be closely related to types A, B and D retroviruses. The HERV-K genomes are present at about 50 copies per haploid human genome. In several human tumor cell lines, the HERV-K genome was expressed as 8.8 kb poly(A)+ RNA which appeared to be a full-size transcript of this genome. In the human breast cancer cell line T47D, stimulation of HERV-K genome expression was observed following female steroids treatment. In a detailed investigation on the organization of HERV-K proviruses in human genome, we found repetitive sequences homologous to the LTR region of the HERV-K genome. They were about 630 bp in length with an A rich tail at 3' end and found to be a SINE type nonviral retroposon. These elements were present at 4,000 to 5,000 copies per haploid human genome.
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PMID:Molecular biology of type A endogenous retrovirus. 171 Jun 82

An agent with the properties of a retrovirus has been detected regularly in monocytes from patients with breast cancer. In 97% of breast cancer patients the cell-free culture medium (CFCM) in which the monocytes had been cultured possessed reverse transcriptase (RT) activity. In contrast, RT activity was detected in the CFCM from only 11% of age and sex matched controls (p less than 0.0001; Wilcoxon rank sum test). The RT activity was associated with particles having a buoyant density of between 1.165 and 1.18 g/ml, similar to that of retroviruses. Treatment of the samples with non-ionic detergent abolished the peaking of the activity in this fraction. Enveloped particles (100-120 nm in diameter) with a fringed surface resembling murine mammary tumour virus were found on negative-stain electron microscopy in CFCM obtained from patients with breast cancer. Retrovirus-like particles were also observed in the cytoplasm of giant cells formed by monocytes from these patients, and also in macrophages in breast cancer tissue; however, no such particles were detected in the tumour cells. These findings strongly suggest the presence of a retrovirus in the monocytes from patients with breast cancer. The importance of these observations in the pathophysiology of carcinoma of the breast remains to be established.
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PMID:Particles with properties of retroviruses in monocytes from patients with breast cancer. 169 2

Particles containing reverse transcriptase activity have been detected in metastatic cells. This suggests that there may be viral particles within the primary tumour. The concept that this virus is oncogenic, and is an aetiological agent in breast cancer is attractive, although presently, there is no evidence of this nor of the mode of viral transmission.
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PMID:Viral involvement in breast cancer. 248 44

Burkitt's lymphomas, linked by previous studies with the DNA-containing Epstein-Barr virus, contain an RNA related in sequence to that of Rauscher leukemia virus. The present study establishes that the viral-related RNA found in Burkitt's tumors is a 70S component encapsulated with RNA-instructed DNA polymerase in a particle possessing a density characteristic of RNA tumor viruses. Further, the DNA synthesized by the Burkitt particles hybridizes specifically to the RNA of Rauscher leukemia virus. Thus, four features characteristic of a known oncogenic RNA agent are also exhibited by particles found with a high (87%) frequency in Burkitt's tumors. The relation between the RNA particle and the Epstein-Barr virus and their etiological roles remains to be elucidated. However, relevant to these issues is the finding reported here that the presence of Epstein-Barr virus information in nonneoplastic cells does not lead to the production of the RNA particles that have been detected now in three different human neoplasias, including leukemias, breast cancer, and Burkitt's disease.
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PMID:Burkitt's tumors contain particles encapsulating RNA-instructed DNA polymerase and high molecular weight virus-related RNA. 412 90

We have recently established four new human breast cancer cell lines that were characterized as being of human mammary origin. We examined these cell lines for particles morphologically resembling retroviruses by electron microscopy, for extracellular and intracellular particles containing high-molecular-weight RNA and RNA-directed DNA polymerase by biochemical assays, and for mouse mammary tumor virus (MMTV)-related sequences in the cell genomes by molecular hybridization. An extensive search for budding particles by thin-section electron microscopy of cells did not provide evidence for retrovirus-like particles. Similarly, 1000- to 2000-fold concentrated samples of medium harvested from 10(8) cells did not contain particles of a density of 1.14 to 1.16 g/ml containing RNA-directed DNA polymerase. Compared with DNA polymerase activity of MMTV, and taking into account the particle weight and protein content of retroviruses, we estimate that, if these cells produce retrovirus-like particles, this production would be less than 1.6 particles/cell every 24 to 72 hr. The hybridization of cell DNA with MMTV complementary DNA also did not show detectable amounts of virus-related sequences in the cell genome. Analysis of the hybridization results suggested that, if the human breast cells contained MMTV-related sequences, they must be present in less than one copy per 100 cells. Thus, we have obtained no convincing evidence for the presence of retrovirus-like particles or subviral components in these cells. It is of course possible that these cells contain virus information but at levels below the sensitivity of our assay procedures.
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PMID:Search for retrovirus-like particles in human breast cancer cells in culture. 616 39

Two DNA polymerases with properties of viral RNA-directed DNA polymerase were found in the placenta of a patient with breast cancer. Both enzyme activities were purified by column-chromatographic procedures or by preparative isoelectric focusing. The most distinguishing feature of the two enzymes is their specificity to transcribe (rA)n . (dT)12 or (rC)n . (dG)18. The two enzymes differ with respect to their elution profiles from the phosphocellulose column, isoelectric point, molecular weight, bivalent-cation requirements and thermal stability. Serological analysis of the (rA)n . (dT)12-activated enzyme showed that this enzyme is immunologically not related to DNA polymerase-gamma, or to any of the reverse transcriptases purified from retroviruses of avian, murine and subprimate origin. However, the activity of this enzyme was neutralized by antibodies to reverse transcriptase purified from human spleen of a patient with myelofibrosis [Chandra & Steel (1977) Biochem. J. 167, 513-524]. Attempts to purify reverse transcriptase of normal human placenta were repeatedly unsuccessful. Once the crude homogenate of normal placenta was freed from endogenous nucleic acids, no (rC)n . (dG)18-dependent activity cold be detected.U
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PMID:Evidence for two forms of reverse transcriptase in human placenta of a patient with breast cancer. Purification and biochemical characterization of the enzymes. 617 35

The expression of a mouse mammary tumor virus is inducible by hormones, and the virus contains a hormone-responsive element. Viral particles and RNA-directed DNA polymerase (RDDP, EC 2.7.7.7; reverse transcriptase) are both detectable in human breast tumors but the frequency and significance of these findings are unknown. Breast tumor biopsy specimens (from either the primary site or a metastasis), frozen in liquid nitrogen at the time of surgery, were routinely obtained to determine estrogen receptor (ERP) concentration. A sample of the tissue was pulverized, homogenized and centrifuged at low speed to remove nuclei and mitochondria. The supernate was then centrifuged at 225,000 g to obtain the cytosol fraction for estrogen and progestin receptor (PgR) assays. Partially purified membranes for the RDDP assays were prepared from the high-speed pellet by discontinuous sucrose density gradient centrifugation. The RDDP assay involved measuring primer-dependent poly(dT) synthesis in the presence of poly(A) as template and oligo-(dT)12-18 as primer. To date, we have studied biopsy specimens from 46 patients with breast cancer. 27 (59%) had ERP and 23 (50%) were RDDP-positive. There was no significant correlation between ERP concentration and RDDP activity. PgR data were available on 36 of the patients; 17 (47%) were positive. No correlation between RDDP and PgR was apparent. Similarly, there was no correlation between RDDP and clinical stage of the disease.
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PMID:RNA-directed DNA polymerase activity in human breast cancer biopsy specimens. Relation to estrogen receptor protein. 620 38

Inappropriate expression of Her-2/neu (ERBB2) gene has been associated with impaired breast cancer prognosis, suggesting a functional role in tumor progression. Herein we describe a quantitative method for analysis of Her-2/neu gene messenger RNA (mRNA), which employs reverse transcriptase polymerase chain reaction (RT-PCR) on a 10-microns cryostat section. The technique combines modified RNA extraction with complementary DNA (cDNA) synthesis to achieve a high level of sensitivity. Utilizing this PCR-based gene expression assay, we were able to quantitate variable amounts of Her-2/neu mRNA in cell lines with established levels of gene expression and in clinical human breast cancer specimens. In clinical samples, mRNA levels correlated with intensity of immunoperoxidase staining for corresponding oncoprotein. We conclude that PCR-based mRNA quantitation can be applied to quantitative analysis of Her-2/neu gene expression, and potentially many other genes, in samples of limited size.
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PMID:Quantitative analysis of Her-2/neu (ERBB2) gene expression using reverse transcriptase polymerase chain reaction. 750 83

The natural plant products turmeric, beta-carotene, catechin, and betel leaf extract were evaluated for their antitumor effects on mammary tumorigenesis in murine mammary tumor expressing C3H (Jax) mice and in Wistar rats treated with the chemical carcinogen 7-12-dimethylbenz(a)anthracene (DMBA). Administration of turmeric through the diet and of beta-carotene, catechin, and betel leaf extract through the drinking water to virgin female C3H mice resulted in decreased tumor incidence and tumor burden. Administering 5% turmeric in the diet from 2 months of age showed suppression of mammary tumor virus-related reverse transcriptase activity and of preneoplastic changes in the mammary glands. Furthermore, feeding turmeric from 6 months of age resulted in a 100% inhibition of mammary tumors. In the DMBA model of rat mammary tumorigenesis, administration of turmeric, catechin, and betel leaf extract resulted in decreased tumor burden and tumor incidence, and a delay in the onset of mammary tumors.
Breast Cancer Res Treat 1994
PMID:Chemoprevention of mammary tumor virus-induced and chemical carcinogen-induced rodent mammary tumors by natural plant products. 752 4

Prostate-specific antigen (PSA) is considered a highly specific biochemical marker of the prostate gland and is currently used for prostate cancer diagnosis and monitoring of patients with prostate adenocarcinoma. We recently demonstrated, however, that about 30% of female breast tumors produce a M(r) 33,000 protein that has striking similarities to seminal PSA. In this study we characterized the presence of PSA in 6 breast tumors and in the testosterone-stimulated T47D breast cancer cell line at the mRNA level. Using reverse transcriptase-polymerase chain reaction and DNA sequencing techniques we identified PSA mRNA in immunoreactive PSA-positive breast tumors but not in immunoreactive PSA-negative breast tumors. The sequence of the generated polymerase chain reaction products was identical to the sequence of the PSA complementary DNA derived from prostate tissue. The data presented here support the notion that breast tumors produce a M(r) 33,000 protein which is identical to PSA produced by the prostate gland. Our study suggests that the presence of PSA in breast tumors may be used as a new additional biochemical marker for breast cancer prognosis, for the spreading of hematogenous micrometastases, and/or for response to adjuvant treatment.
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PMID:Molecular characterization of prostate-specific antigen messenger RNA expressed in breast tumors. 752 95


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