Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The induction of cell death along with cell-cycle arrest is one of the foremost mechanisms regulating cell growth. In the human breast carcinoma cell line MCF-7 we investigated two chemotherapeutic agents, the antiestrogen tamoxifen and the DNA-damaging drug cisplatin, for the relative contribution of these mechanisms to growth inhibition in culture. Growth kinetics and flow cytometry confirmed that tamoxifen at 1 microM acts mainly by arresting cells in the G0/G1 phase of the cell cycle. Compared to untreated controls, only a few more cells were detached from the monolayer and dead after a 5-day incubation. On the other hand, cisplatin at 1 microM did not induce the well-defined G2/M-arrest reported for other cell types, but resulted in a marked increase in the rate of cell death. A morphological feature observed, especially with cisplatin-treated MCF-7 cells, was the formation of numerous micronuclei (in up to 30% of the cells) and an increase in the number of binucleate cells (up to 20%). In both tamoxifen- and cisplatin- treated cultures, cell death appeared to occur by apoptosis, as indicated morphologically by cellular and nuclear shrinkage accompanied by DNA-condensation and ultimately the formation of DNA containing apoptotic bodies. However, no internucleosomal DNA degradation or endogenous endonuclease activity could be detected in the cells of the monolayer or in the mainly dead and detached cells of the culture supernatant. DNA fragmentation was only observed when isolated MCF-7 nuclei were incubated with exogenous endonucleases. However, as determined by reverse transcriptase/polymerase chain reaction amplification, MCF-7 cells do express the mRNA for DNase I, an endonuclease known to be involved in apoptosis. Thus, apoptosis is part of the growth-inhibitory process and occurs without apparent internucleosomal DNA fragmentation in MCF-7 cell cultures.
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PMID:Cell-cycle arrest, micronucleus formation, and cell death in growth inhibition of MCF-7 breast cancer cells by tamoxifen and cisplatin. 887 58

The growth of tumor cells can be regulated by a variety of cytokines. To investigate the pathogenesis of choriocarcinoma and explore a new therapeutic approach for the carcinoma, we examined the role of IL-6 in the growth of a human choriocarcinoma cell line (JEG-3). IL-6 was identified in the supernatant of the cell culture medium by enzyme-linked immunosorbent assay, indicating that this cell secreted IL-6. The mRNAs of IL-6, IL-6 receptor and gP130, the IL-6 signal transducer, in this cell were shown to be present by reverse transcriptase polymerase chain reaction assay and confirmed by Southern blot hybridization and direct sequencing. The addition of hrIL-6 to the cell culture failed to stimulate cell growth. Monoclonal antibodies against IL-6, IL-6 receptor, and gP130 were also unable to inhibit the proliferation of this cell line. The antisense oligonucleotides targeting IL-6 mRNA, however, inhibited both cell growth and IL-6 production. Taken together, these findings indicate that endogenous IL-6 plays an important role in the growth of the JEG-3 cell line, and it exerts its action by an intracellular autocrine growth mechanism. The results also suggest that the therapeutic trials with monoclonal antibodies designed to neutralize IL-6 or block its receptor will likely fail, whereas the antisense oligonucleotides targeted to IL-6 mRNA may have some value for the treatment of choriocarcinoma and other cancers with intracellular autocrine growth fashion mediated by IL-6.
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PMID:IL-6 antisense-mediated growth inhibition of a choriocarcinoma cell line: an intracellular autocrine growth mechanism. 889 73

Nasal T/NK-cell lymphomas can be further separated into those of natural killer (NK) cell lineage or of T-cell lineage, with differences in cellular phenotype, T-cell receptor (TcR) gene rearrangement and TcR transcript expression. Both NK- and T-cell subtypes are closely associated with Epstein-Barr virus (EBV). In this study, EBV gene expression was determined in 23 cases of nasal lymphoma (NL) by in situ hybridisation (ISH), reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IH). Of the 23 cases, 19 were classified as NK-cell and 4 as T-cell tumours. ISH for EBV-encoded small non-polyadenylated RNAs showed that all cases, whether NK or T, harboured EBV in virtually all tumour cells. RT-PCR demonstrated that NL of both subtypes expressed EBNAI of the QUK splice pattern, the latent membrane proteins, LMP1 and 2 and the BamHI A rightward transcripts in the absence of EBNA2 mRNAs, compatible with the latency type II pattern. In addition, analysis of EBV protein expression by IH revealed a heterogeneous pattern of EBV gene expression at the single-cell level consisting of both LMP1+ and LMP1- tumour cells, suggesting a mixture of latency I and II. Although 2 early lytic transcripts, BZLF1 and BHRF1, were also detected in 13 and 10 cases, respectively, the lack of ZEBRA staining in any case indicates that these lytic transcripts are most likely expressed by rare cells in the biopsies entering lytic cycle. The viral transcriptional pattern similar to that of nasopharyngeal carcinoma and Hodgkin's disease suggests that EBV can exploit common regulatory mechanisms for gene transcription in diverse host cell types. Down-regulation of immunogenic proteins (EBNA2-EBNA6) in nasal lymphoma may enable tumour cells to evade host cytotoxic T-cell surveillance.
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PMID:Nasal NK- and T-cell lymphomas share the same type of Epstein-Barr virus latency as nasopharyngeal carcinoma and Hodgkin's disease. 890 67

The object of this study was to investigate the influence of reactive oxygen intermediates (ROI), such as H2O2, on HIV-1 infection of cell cultures. The CD4+ HeLa human epithelial carcinoma cell line clone pBKTRLac was infected with HIV-1MN that had been treated with 0.01-5mM H2O2. Virus infectivity was detected by 3 methods: (a) using transactivation of LTR-linked beta-Galactosidase, (b) viral core p24 antigen enzyme-linked immunoasorbent assay (ELISA), and (c) reverse transcriptase activity assay. Treatment of HIV-1MN cell free virus particles with 0.01 mM H2O2 resulted in a significant increase in virus infection. This effect declined with increasing H2O2 concentrations from 0.05 to 0.1 mM. Further increases in H2O2 concentration up to 5 mM resulted in significant suppression in virus infection. These observations indicate that H2O2 may play a role in affecting the course of HIV infection.
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PMID:Influence of hydrogen peroxide on the in vitro infectivity of human immunodeficiency virus. 890 98

In this study, we provide the first report on the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by human thyroid epithelial cells. Primary cultures of highly purified thyrocytes and thyroid-derived fibroblasts (n = 3) and three thyroid anaplastic and one largely papillary carcinoma cell lines were exposed to different potent GM-CSF stimulators, employing interleukin 1 alpha (Il-1 alpha) and tumour necrosis factor-alpha (TNF-alpha). Cytokine mRNA levels were monitored by semi-quantitative reverse transcriptase-PCR including an internal heterologous competitor fragment after 3, 6 and 18 h of culture. Culture supernatants were assayed for GM-CSF using a highly sensitive ELISA (detection limit < or = 0.5 pg/ml) after 24 h. Basal GM-CSF mRNA expression was higher in fibroblasts and SW 1736 cells compared with thyrocytes, C 634, 8505 C and HTh 74 cells. GM-CSF was spontaneously secreted by fibroblasts (means +/- S.E.M.; 43 +/- 15 pg/ml), SW 1736 (59 +/- 4 pg/ml), HTh 74 (34 +/- 4 pg/ml) and C 643 cells (12 +/- 1 pg/ml) but not by thyrocytes and 8505 C cells. Treatment with Il-1 alpha (10 U/ml) resulted in a marked increase of GM-CSF mRNA within 3 h and an increase or induction of protein expression in thyrocyte (2350 +/- 214 pg/ml), fibroblast (5242 +/- 1400 pg/ml), SW 1736 (20016 +/- 280 pg/ml) and C 643 cultures (1285 +/- 79 pg/ml). Stimulation with TNF-alpha (10 U/ml) yielded divergent results. No significant increase of GM-CSF mRNA or protein expression was found in thyrocytes although TNF-alpha receptor expression in these cells is well documented. Stimulation with TNF-alpha resulted in an increased GM-CSF production in fibroblasts (361 +/- 14 pg/ml), HTh 74 (148 +/- 51 pg/ml) and SW 1736 cultures (235 +/- 43 pg/ml). TSH (10 mU/ ml) did not stimulate GM-CSF secretion in thyrocytes and HTh 74 cells, both expressing the TSH receptor. Phorbol 12-myristate 13-acetate (10 ng/ml) enhanced GM-CSF mRNA and protein levels in all cell types investigated. Our data suggest that both thyrocytes and fibroblasts synthesize GM-CSF in response to Il-1 alpha, but only fibroblasts respond to TNF-alpha with a significant increase in GM-CSF. Anaplastic thyroid carcinomas are potential GM-CSF producers.
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PMID:Differential regulation of granulocyte-macrophage colony-stimulating factor mRNA and protein expression in human thyrocytes and thyroid-derived fibroblasts by interleukin-1 alpha and tumor necrosis factor-alpha. 895 88

Lymphoproliferative disorders involving Epstein-Barr virus (EBV) infected natural killer (NK) cells are reported with increasing frequency, but the nature and role of EBV infection in these cells remains undefined. In this study, we have investigated virus-cell interactions in the EBV-positive YTN10 cell line, an NK-like cell line established from a patient with lymphoblastic lymphoma. Low level expression of the EBV receptor CD21 molecule was detected by FACS and reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Immunoblotting and RT-PCR analysis identified a latency II pattern of EBV gene expression, consisting of EBNA-1 transcription from the Qp promoter, in the absence of other EBNA gene expression, and accompanied by LMP-1 and LMP-2A expression. The EBV genome was present in episomal form and there was evidence for lytic viral replication. This latency pattern is typical of EBV gene expression in nasopharyngeal carcinoma and Hodgkin's disease, and differs from the full spectrum of EBV latent gene expression in most posttransplant lymphoproliferative disorders and from the restricted EBNA-1 expression in Burkitt's lymphoma tissues. The interaction between EBV and NK cells described here has important implications for the pathogenesis and treatment of EBV-infected NK malignancies.
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PMID:Virus-cell interactions in a natural killer-like cell line from a patient with lymphoblastic lymphoma. 897 60

Detection of the mRNA of selected genes by reverse transcriptase-polymerase chain reaction (RT-PCR) is a sensitive and powerful tool for detecting cancer cells in bone-marrow or peripheral-blood samples. In this study, we determined whether carcinoembryonic antigen (CEA) mRNA is detectable in the peripheral blood of patients with gastrointestinal or breast cancer. In addition, we studied selected patients undergoing surgical procedures to assess whether tumor manipulation during operation enhances cancer-cell dissemination. Peripheral blood from 55 patients with gastrointestinal or breast cancer and from 22 control cases was analysed for CEA mRNA using RT-PCR. For 15 selected cases undergoing curative surgery for cancer, samples were also obtained during and after surgery. The lower limit of detection was 1 to 10 CEA-positive cells diluted among 1 x 10(7) blood mononuclear cells. The test was positive for 20 of the 55 patients with cancer (36%). None of the 22 control samples were positive. An increase in positivity was observed with increasing stage of disease; however, even some patients with early-stage cancer showed positive results. In addition, CEA mRNA could be detected in the peripheral blood during operation in 3 of 13 patients whose pre-operative CEA mRNA in the peripheral blood had been negative. These findings suggest that, (1) RT-PCR amplification of CEA mRNA is an efficient means of detecting circulating solid cancer cells in the peripheral blood, although long-term clinical studies should be done to evaluate its usefulness; (2) not only breast cancer but also gastrointestinal cancer might be better regarded as a systemic disease even in early stages of carcinoma; and (3) surgical manipulation can provoke cancer-cell dissemination.
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PMID:Molecular detection of circulating solid carcinoma cells in the peripheral blood: the concept of early systemic disease. 898 Jan 76

Interleukin (IL)-6 plays a significant role in genitourinary carcinomas. The present study was conducted to define the role of IL-6 in the growth of prostatic carcinoma and benign prostatic hyperplasia (BPH). An in vitro experiment was carried out using human prostatic carcinoma cell lines (LNCaP, which is androgen sensitive and slow growing, and DU145 and PC3, which are androgen insensitive and fast growing), and primary human epithelial and stromal cells derived from BPH. Cells were treated with recombinant human IL-6 or conditioned medium (CM) derived from the above cultured cells to identify possible paracrine and autocrine pathways. LNCaP was clearly responsive to exogenous IL-6 and to the CM derived from stromal cells, but not to the CM from LNCaP cells (P < 0.001). DU145 and PC3 were slightly stimulated to grow by exogenous IL-6 and the CM derived from both stromal and respective homologous cells (P < 0.01). In contrast, BPH-derived epithelial cells showed little or no response to IL-6. The stimulatory effect of CM on prostatic carcinoma cells was significantly reduced by the addition of anti-IL-6 antibody to the culture medium. Furthermore, the growth of DU145 and PC3 in serum-free medium was also inhibited by anti-IL-6 antibody (P < 0.001). All cell lines tested, except for LNCaP, secreted IL-6 into the culture medium. Results of reverse transcriptase-PCR analysis indicated that IL-6 receptor mRNA was present in all carcinoma cell lines but not in epithelial cells or stromal cells derived from BPH. These results suggest that IL-6 functions as a paracrine growth factor for LNCaP and as an autocrine growth factor for DU145 and PC3, but it has no stimulatory effect on epithelial cells derived from BPH.
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PMID:Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro. 898 55

Hashimoto's thyroiditis is an inflammatory disease of the thyroid gland with autoimmune etiology. Patients afflicted with Hashimoto's have a higher risk of thyroid malignancies such as papillary thyroid carcinoma. In the present study, we investigated the frequency of papillary thyroid carcinoma specific genes in patients diagnosed with Hashimoto's disease. The newly identified oncogenes RET/PTC1 and RET/PTC3 provide useful and specific markers of the early stages of papillary carcinoma as they are highly specific for malignant cells. Using a sensitive and specific reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we found messenger RNA (mRNA) expression for the RET/PTC1 and RET/PTC3 oncogenes in 95% of the Hashimoto's patients studied. All Hashimoto's patients presenting without histopathologic evidence of papillary thyroid cancer showed molecular genetic evidence of cancer. These data suggest that multiple, independent occult tumors exist in these patients at high frequency.
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PMID:Expression of the RET/PTC fusion gene as a marker for papillary carcinoma in Hashimoto's thyroiditis. 1036

The costimulatory signal through CD80 or CD86 to its counterreceptor CD28 or CTLA-4 on T cells has been shown to play an important role in the induction of T-cell-mediated immunity against tumors. In the present study, we examined the expression of CD80 and CD86 in the cell lines derived from human gastric, esophageal and colorectal carcinomas at the mRNA level, by means of a reverse transcriptase/polymerase chain reaction analysis and, for their surface expression, using a flow-cytometric analysis with monoclonal antibodies (mAb). The expression of mRNA for CD80 or CD86 was detected in all 18 cell lines tested, except for CD86 on one cell line. The cells from 13 (72%) or 12 (67%) of these cell lines expressed the surface CD80 or CD86 molecule, detected with the respective mAb. The surface expression of CD80 or CD86 was increased in four to five of the six cell lines tested after a culture with interferon gamma (IFN gamma). In addition, the up-regulation of CD80 or CD86 expression by IFN gamma was inhibited by interleukin-10 (IL-10). These results indicated that, in the cell lines derived from human gastrointestinal carcinoma, both the costimulatory molecules CD80 and CD86 were detectable in the majority of the cell lines examined at the mRNA and protein levels, and could be regulated with the cytokine IFN gamma or IL-10.
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PMID:The expression of costimulatory molecules CD80 and CD86 in human carcinoma cell lines: its regulation by interferon gamma and interleukin-10. 900 66


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