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 c-myc proto-oncogene is a reliable marker of the "G0-early G1" transition, and its down-regulation is believed to be necessary to obtain cellular differentiation. In murine spermatogenesis, the level of c-myc transcripts does not correlate with the rate of cellular division. Proliferation of supposed staminal spermatogonia to reproduce themselves is induced with a local 5 Gy X-ray dose in 90-day-old C57Bl/6 mice. c-myc quantification by a newly developed competitive reverse transcriptase polymerase chain reaction (RT-PCR) was carried out to follow the expression course of this proto-oncogene. Damage and restoration of spermatogenesis were analyzed at days 3, 6, 9, 10, 13, 30, and 60 after injury by relative testes/body weight determination and histological examination. Proliferative status was determined by histone H3 Northern blot analysis. c-myc mRNA level was 10 times higher after 3 days in the irradiated animals compared to the controls. An increasing number of copies were noted up to 10 days, but promptly decreased to the base level found for irradiated mice from 13 to 60 days. Interestingly, the expression of histone H3 detected S phase only in testes at 60 days from damage.
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PMID:Course of c-myc mRNA expression in the regenerating mouse testis determined by competitive reverse transcriptase polymerase chain reaction. 753 36

Stage-specific expression of proto-oncogenes, including c-myc, has been demonstrated during spermatogenesis in testis. Some of these proto-oncogenes are expressed postmeiotically, especially in the round spermatid stage. Recently, we demonstrated the presence of c-myc protein in mature ejaculated sperm cells with a possible role in sperm cell function. Since the half-life of c-myc protein has been shown to be short, we suspected the presence of c-myc mRNA in human sperm cells. In the present study, the presence of the c-myc mRNA transcript in human sperm cells was investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and in situ hybridization. Total RNA, 5-10 micrograms, was extracted from 0.2-0.5 ml of pelleted human sperm cells by NP-40 lysis procedure, and was used to construct cDNA with pd(N)6 random primer and Moloney Murine Leukemia Virus (MMLV) reverse transcriptase. The PCR with sperm cDNA and primers #P1 and #P2, both from exon 3, resulted in amplification of the expected 322 bp product. Primers #P3 and #P4, which are located in exon 2 and exon 3, respectively, and are 1.37 kb apart, gave the expected PCR amplified 313 bp product ruling out the possibility of DNA contamination. The presence of c-myc mRNA in human sperm cells was further confirmed by in situ hybridization using a digoxigenin labelled DNA probe, containing exon 2 of the c-myc gene sequence. The c-myc specific DNA probe reacted with the postacrosomal mid-piece and tail regions of both noncapacitated as well as capacitated methanol-fixed sperm cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:c-MYC mRNA is present in human sperm cells. 822 May 81

In this study, we investigated the c-myc expression by tonsillar germinal center (GC) B cells using reverse transcriptase-polymerase chain reaction, flow cytometry, Western blot and in situ immunohistochemical methods. The results obtained demonstrate elevated levels of c-myc mRNA and of Myc protein in GC B cells compared to those of the other resting or activated tonsillar B cells. Separation of GC B cells into centroblasts and centrocytes revealed that, while differing in their cell cycle status, surface marker expression and morphology, the two cell types had the same propensity to apoptosis and elevated Myc protein expression, thus reinforcing the notion of a close correlation between these two events. Based upon these observations and other considerations it is proposed that elevation of Myc proteins confers to GC B cells a particular propensity to apoptosis, while the subsequent decision between progression into the cell cycle or programmed cell death is dictated by other signals that are delivered in the GC and perhaps operate at the level of other proto-oncogenes.
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PMID:The propensity to apoptosis of centrocytes and centroblasts correlates with elevated levels of intracellular myc protein. 902 24

The erythromegakaryocytic cell line (LAMA-84) and the erythroeosinophilic cell line (LAMA-87) were used to study receptor expression and receptor-mediated response to monocyte/macrophage colony-stimulating factor (M-CSF) and transforming growth factor beta (TGF-beta), two modulators of cell proliferation. As demonstrated by Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR), c-fms and M-CSF mRNA were expressed in both cell lines. M-CSF was detected in the supernatant of both cell lines and addition of a neutralizing anti-M-CSF antibody inhibited cell growth. The two LAMA cell lines were found to express TGF-beta1, -beta2, and -beta3 mRNAs and to secrete TGF-beta mostly in latent form. Addition of anti-TGF-beta antibodies to the culture medium increased their proliferation, whereas TGF-beta1 inhibited cell proliferation by downregulating the c-myc mRNA. These results show that the proliferation of both LAMA cell lines is positively and negatively regulated by autocrine mechanisms, implying the presence of M-CSF and TGF-beta, respectively. They suggest that similar autocrine loops could be involved in the growth regulation of leukemic cells in vivo.
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PMID:Proliferation of LAMA-84 and LAMA-87 cell lines is modulated by autocrine loops involving M-CSF and TGF-beta. 925 9

To clarify the prognostic value of the c-myc oncogene mRNA expression levels in human colorectal cancer, samples obtained from 35 surgically resected tissues were examined by the semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Overexpression of c-myc mRNA was detected in 22 cases (63%). Although there was no correlation between c-myc overexpression and the depth of invasion, lymph node metastasis, or Dukes' stage, the patients with c-myc overexpression had metastatic recurrences significantly more frequently than those without it (29% versus 0%, p<0.05). The disease-free survival rate at 5 years was significantly lower in patients with c-myc overexpression than in those without it (70% versus 100%, p<0.05). These results demonstrate that c-myc mRNA overexpression as assessed by semi-quantitative RT-PCR may be a useful prognostic indicator in patients with colorectal cancer.
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PMID:Prognostic significance of c-myc mRNA expression assessed by semi-quantitative RT-PCR in patients with colorectal cancer. 946 76

In addition to its inhibitory activity against viral DNA polymerases and reverse transcriptase, the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA) also markedly inhibits the replicative cellular DNA polymerases alpha, delta, and epsilon. We have previously shown that PMEA is a strong inducer of differentiation in several in vitro tumor cell models and has marked antitumor potential in vivo. To elucidate the molecular mechanism of the differentiation-inducing activity of PMEA, we have now investigated the effects of the drug on cell proliferation and differentiation, cell cycle regulation, and oncogene expression in the human erythroleukemia K562 cell line. Terminal, irreversible erythroid differentiation of PMEA-treated K562 cells was evidenced by hemoglobin production, increased expression of glycophorin A on the K562 cell membrane, and induction of acetylcholinesterase activity. After exposure to PMEA, K562 cell cultures displayed a marked retardation of S-phase progression, leading to a severe perturbation of the normal cell cycle distribution pattern. Whereas no substantial changes in c-myc mRNA levels and p21, PCNA, cdc2, and CDK2 protein levels were noted in PMEA-treated K562 cells, there was a marked accumulation of cyclin A and, most strikingly, cyclins E and B1. A similar picture of cell cycle deregulation was also observed in PMEA-exposed human myeloid THP-1 cells. However, in contrast to the strong differentiation-inducing activity of PMEA in K562 cells, the drug completely failed to induce monocytic maturation of human myeloid THP-1 cells. On the contrary, THP-1 cells underwent apoptotic cell death in the presence of PMEA, as demonstrated by prelytic, intracellular DNA fragmentation and the binding of annexin V to the cell surface. We hypothesize that, depending on the nature of the tumor cell line, PMEA triggers a process of either differentiation or apoptosis by the uncoupling of normally integrated cell cycle processes through inhibition of DNA replication during the S phase.
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PMID:9-(2-Phosphonylmethoxyethyl)adenine induces tumor cell differentiation or cell death by blocking cell cycle progression through the S phase. 1039 5

Lung tumors frequently exhibit altered expression of oncogenes and/or tumor suppressor genes. Although some of these alterations are believed to arise from chemical exposure, the ability of specific chemicals to cause distinct changes in gene expression is not well characterized. We previously reported the development of a quantitative reverse transcriptase/polymerase chain reaction (RT/PCR) method for measuring c-myc mRNA levels, and reported that c-myc proto-oncogene expression is significantly increased in small-cell lung carcinoma cells. In the present study, quantitative RT/PCR was used to assess the effect of model toxins cycloheximide (CHX), a protein synthesis inhibitor, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a DNA alkylating agent, on c-myc mRNA levels in normal human bronchial epithelial (NHBE) and lung adenocarcinoma (A549) cells. Expression of c-myc was evaluated at 1-100 microM CHX and MNNG and was compared to the cytotoxic response as measured by the neutral red assay. Cycloheximide elicited a dose-dependent increase in c-myc mRNA levels in NHBE and A549 cells, but did not alter expression of the housekeeping gene beta-actin. A maximum increase for c-myc expression (200% of control) was observed 5 h after treatment with noncytotoxic concentrations. In contrast, MNNG elicited a dose-dependent decrease in c-myc expression in A549 cells, but no significant change in c-myc was observed in NHBE cells. The results from this study suggest that the quantitative RT/PCR method may be an appropriate technique for monitoring gene expression changes following chemical exposure. Hence, these types of studies may assist in the identification of specific chemicals which may induce the genetic alterations involved in the development of lung cancer as well as provide information relevant to the interactive effects of chemicals within complex mixtures.
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PMID:Quantification of changes in c-myc mRNA levels in normal human bronchial epithelial (NHBE) and lung adenocarcinoma (A549) cells following chemical treatment. 1150 50

Proteasome inhibitors were shown previously to induce mitochondria-independent and caspase-3-dependent apoptosis in human glioma cell lines by unknown mechanisms. Here, we showed that treatment with proteasome inhibitors, lactacystin or acetyl-leucinyl-leucinyl-norleucinal, led to elevation of the steady-state c-Myc protein but not c-myc mRNA, suggesting the accumulation of c-Myc protein by proteasome inhibitors. In addition, the marked association of c-Myc protein with ubiquitin by treatment with proteasome inhibitors indicated the involvement of proteasome in c-Myc proteolysis and the stabilization of c-Myc protein by proteasome inhibitors in vivo. The expression of Fas (also termed CD95 or APO-1) mRNA, if analyzed by reverse transcriptase polymerase chain reaction assay, was found to occur constitutively, and increased slightly by the treatment with proteasome inhibitors. In contrast, the expression of Fas ligand (FasL) mRNA was markedly induced temporarily before the activation of caspase-3 by the treatment. Agonistic anti-Fas antibody (CH11) induced apoptotic cell death, suggesting the presence of a functional Fas receptor. In addition, proteasome inhibitor-induced apoptosis was prevented by the addition of antagonistic anti-FasL antibody (4A5) or z-IETD.fmk, a potent inhibitor of caspase-8, indicating the involvement of the Fas receptor-ligand apoptotic signaling system in proteasome inhibitor-mediated apoptosis. Thus, it is suggested that proteasome inhibitors cause the accumulation of c-Myc protein which induces transiently FasL message to stimulate the Fas receptor-ligand apoptotic signaling pathway.
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PMID:Proteasome inhibitors induce Fas-mediated apoptosis by c-Myc accumulation and subsequent induction of FasL message in human glioma cells. 1152 96

Human telomerase is a specialized reverse transcriptase that catalyses telomeric repeat addition at the ends of chromosomes. Activation of this enzyme is one of the key steps in cell immortalization and carcinogenesis, and one of its components, hTERT, is considered as the rate-limiting factor. While telomerase activity was found to be prognostically relevant in various cancers, results obtained from renal cell carcinomas (RCC) failed to show any correlation with the usual prognostic factors. The aim of the study was to reassess the role of telomerase and its hTERT component in the biological behaviour of RCC using new quantitative techniques, such as the quantitative evaluation of hTERT mRNA level by a real-time RT-PCR procedure and the measuring of telomerase activity by an ELISA TRAP assay. Since experimental evidence supports a relationship between cell proliferation or c-myc expression and telomerase, the proliferation index and c-myc mRNA levels were also studied. Forty-one RCC (29 conventional renal cell carcinomas (CRCC), 10 papillary RCC and two urothelial carcinomas) were studied. In 73% of cases, normalized hTERT mRNA expression was significantly higher in the tumour sample than in the normal tissue. Telomerase activity was detected in 63% of RCC, while corresponding normal tissue was always negative. Analysis of correlations showed firstly that both telomerase activity and hTERT mRNA level were lower in the group of CRCC versus non-CRCC (TRAP: 0.3+/-0.1 versus 0.6+/-0.2, p<0.05; hTERT/PO mRNA: 5+/-3 versus 37+/-8, p<0.001, respectively); secondly, that in the group of CRCC, hTERT mRNA expression level was correlated with the stage of the tumour (p=0.01); and thirdly, that no correlation was observed between c-myc mRNA level and hTERT mRNA level. In conclusion, these results support the involvement of telomerase in RCC and the potential interest of hTERT mRNA quantification.
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PMID:hTERT expression in sporadic renal cell carcinomas. 1159

A Coding Region instability Determinant-Binding Protein (CRD-BP) binds in vitro to c-myc mRNA and appears to stabilize the mRNA. The CRD-BP gene is amplified in one-third of human breast cancer cases, and the CRD-BP appears to be an oncofetal protein. To analyse CRD-BP expression in human cancer tissue, paired extracts of cancer and normal colon specimens from 21 patients were analysed by immunoblotting and/or reverse transcriptase-polymerase chain reaction. Seventeen cancer specimens out of 21 (81%) were positive for CRD-BP expression by one or both assays. With one exception, normal colon specimens were negative for CRD-BP expression; specimens of inflammatory bowel and a villous adenoma also had no detectable CRD-BP. The lack of CRD-BP expression in normal colon did not result from indiscriminate protein or RNA degradation. c-myc mRNA levels appeared to be elevated in tumor specimens. We conclude that the CRD-BP is scarce or absent from normal colon but is overexpressed in colorectal cancer. The CRD-BP might be a novel human tumor marker.
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PMID:Overexpression of an mRNA-binding protein in human colorectal cancer. 1164 79


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