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)

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine considered to play a key role in beta-cell destruction in insulin-dependent diabetes mellitus (IDDM). Serum thymic factor (Facteur thymique serique; FTS) is a nonapeptide thymus hormone known to inhibit IDDM in a mouse model. In this study, the effect of TNF-alpha on the murine pancreatic beta-cell line MIN6 was examined. Cell shrinkage and detachment were seen in cells treated with 0-50 ng/ml TNF-alpha for 12h. Oligonucleosomal DNA fragmentation was determined from non-adherent cells, indicating that the TNF-alpha-induced cell destruction was attributed to apoptosis. Fragmented DNA was quantified by enzyme-linked immunosorbent assay to measure the amount of histone-bound oligonucleosomes. FTS was treated with TNF-alpha and the percentage of fragmented DNA was analyzed. The data indicate a distinct reduction of fragmented DNA at a concentration of 1 ng/ml FTS. Expression of TNF receptor I, inducible form of nitric oxide synthase (iNOS), interleukin-1 beta-converting enzyme (ICE), Bcl-2, and nuclear factor kappa B (NF-kappa B) was analyzed by reverse transcriptase-polymerase chain reaction to investigate the suppressor mechanism of FTS on TNF-alpha-induced apoptosis. FTS treatment suppressed the expression of iNOS and Bcl-2 mRNA in TNF-alpha-treated cells. The expression of NF-kappa B mRNA in TNF-alpha-treated cells was enhanced after FTS treatment, while that of ICE mRNA did not change in TNF-alpha-treated cells with or without FTS treatment. These results suggest that the inhibition of MIN6 cell death by FTS on TNF-alpha-induced apoptosis is caused by a negative feedback mechanism involving the inhibition of iNOS induction.
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PMID:Suppressor mechanism of serum thymic factor on tumor necrosis factor-alpha-induced apoptosis in the mouse pancreatic beta-cell line. 1459 44

Telomerase plays a role in the unlimited replicative capacity of the majority of cancer cells and provides a potential anticancer target. The regulation of telomerase is complex but transcriptional control of its two essential components, hTERC (RNA component) and hTERT (reverse transcriptase component), is of major importance. To investigate this further, we have used the adenoviral protein, E1A, as a tool to probe potential pathways involved in the control of telomerase transcription. The second exon of the adenoviral protein E1A activates both telomerase gene promoters in transient transfections. The corepressor, C terminal binding protein, is one of only two proteins known to bind to this region, and we propose that E1A activates both promoters by sequestering CtBP, thereby relieving repression. Activation by exon 2 of E1A involves the SP1 sites in both promoters, and consistent with this, SP1 and CtBP interact in coimmunoprecipitation studies. Modulation of the chromatin environment has been implicated in the regulation of hTERT transcription and appears to involve the SP1 sites. CtBP can be found within a histone-modifying complex and it is possible that a CtBP complex, associating with the SP1 sites, represses transcription from the telomerase promoters by modifying chromatin structure.
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PMID:The hTERT and hTERC telomerase gene promoters are activated by the second exon of the adenoviral protein, E1A, identifying the transcriptional corepressor CtBP as a potential repressor of both genes. 1603 12

Estrogen is well-established as a mitogenic factor implicated in the tumorigenesis and progression of breast cancer via its binding to the estrogen receptor alpha (ERalpha). Recent data indicate that chromatin inactivation mediated by histone deacetylation (HDAC) and DNA methylation is a critical component of ERalpha silencing in human breast cancer cells. The aim of this study was to determine the expression of the HDAC1 gene in malignant human breast tissue and to correlate our observations with available clinical information. In the present study, the level of expression of HDAC1 mRNA was assessed by LightCycler-based quantitative real-time reverse transcriptase (RT)-PCR analysis in 162 cases of invasive carcinoma of the breast. Associations between HDAC1 mRNA expression and different clinicopathological factors were sought. It was found that HDAC1 mRNA was expressed at significantly higher levels in tumors from patients over 50 years of age and in those tumors without axillary lymph node involvement, that are less than 2 cm, that are of a non-high histological grade, that are HER2 negative and that are ERalpha/PgR positive. Patients with tumors displaying high levels of HDAC1 mRNA expression tended to have a better prognosis in terms of both disease-free and overall survival. However, univariate and multivariate analysis did not show HDAC1 mRNA expression level to be an independent prognostic factor for either disease-free or overall survival. These results imply that HDAC1 mRNA expression could have potential as an endocrine response marker and may have prognostic implications for breast cancer progression.
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PMID:Quantitation of HDAC1 mRNA expression in invasive carcinoma of the breast*. 1617 92

Histones are the building units of nucleosomes and play essential roles in DNA replication, repair and transcription. A comprehensive analysis of histone genes revealed that the Plasmodium falciparum genome encodes a canonical form of each core histone and four histone variants H2A.Z, H3.3, centromere-specific H3 (CenH3), and H2Bv. Mass spectrometry confirmed the synthesis of all histones except CenH3. Real-time reverse transcriptase-polymerase chain reaction and immunoblotting detected a dramatic increase in core histone gene expression during the late trophozoite stages, consistent with their role in replication-related nucleosome assembly. In contrast, the expression of variant histones decreased in mid- or late trophozoite stages. The N-terminal tails of histones participate in transcription regulation through covalent modifications, especially at the lysine residues. In accordance, mass spectrometry analysis revealed acetylation of lysines and methylation of lysines and arginines in the N-termini of H3, H3.3, and H4. Moreover, we identified a new pattern of lysine modifications of the H2A.Z variant. Using a panel of acetylation-specific antibodies, we found that K5, K8, and K12 of H4 were abundantly acetylated at a relatively steady level throughout the erythrocytic cycle. In comparison, the H3-K9 acetylation increased in late trophozoite and schizont stages, while H4-K16 acetylation peaked in mid-trophozoite stage. We have also shown that despite the sequence divergence in the PfH3 N-terminus from their mammalian homologues, the recombinant PfH3 was still efficiently acetylated by both recombinant and native PfGCN5 at K9 and K14. This study suggests that histone replacement and the dynamic histone modifications play important roles in regulating gene expression during erythrocytic development of the malaria parasite.
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PMID:The malaria parasite Plasmodium falciparum histones: organization, expression, and acetylation. 1641 41

Ras-related, estrogen-regulated, and growth-inhibitory gene (RERG) is a novel gene that was first reported in breast cancer. However, the functions of RERG are largely unknown in other tumor types. In this study, RERG expression was analyzed in hepatocellular carcinomas of human patients using reverse transcriptase PCR analysis. In addition, the possible regulation of RERG expression by histone deacetyltransferases (HDACs) was studied in several cell lines. Interestingly, the expression of RERG gene was increased in hepatocellular carcinoma (HCC) of male patients (57.9%) but decreased in HCC of females (87.5%) comparison with paired peri-tumoral tissues. Moreover, RERG gene expression was increased in murine hepatoma Hepa1-6 cells, human breast tumor MDA-MB-231 cells, and mouse normal fibroblast NIH3T3 cells after treated by HDAC inhibitor, trichostatin A. Our results suggest that RERG may function in a gender-dependent manner in hepatic tumorigenesis and that the expression of this gene may be regulated by an HDAC-related signaling pathway.
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PMID:Expression of the RERG gene is gender-dependent in hepatocellular carcinoma and regulated by histone deacetyltransferases. 1704 25

Medulloblastoma is a heterogeneous pediatric brain tumor with significant therapy-related morbidity, its five-year survival rates ranging from 30% to 70%. Improvement in diagnosis and therapy requires better understanding of medulloblastoma pathology. We used whole-genome microarray analysis to identify putative tumor suppressor genes silenced by epigenetic mechanisms in medulloblastoma. This analysis yielded 714 up-regulated genes in immortalized medulloblastoma cell line D283 on treatment with histone deacetylase (HDAC) inhibitor trichostatin A (TSA). Dickkopf-1 (DKK1), a Wnt antagonist, was found to be up-regulated on HDAC inhibition. We examined DKK1 expression in primary medulloblastoma cells and patient samples by reverse transcriptase PCR and found it to be significantly down-regulated relative to normal cerebellum. Transfection of a DKK1 gene construct into D283 cell lines suppressed medulloblastoma tumor growth in colony focus assays by 60% (P < 0.001). In addition, adenoviral vector-mediated expression of DKK1 in medulloblastoma cells increased apoptosis fourfold (P < 0.001). These data reveal that inappropriate histone modifications might deregulate DKK1 expression in medulloblastoma tumorigenesis and block its tumor-suppressive activity.
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PMID:Dickkopf-1 is an epigenetically silenced candidate tumor suppressor gene in medulloblastoma. 1732 7

Rituximab is a chimeric monoclonal antibody to the surface antigen CD20 and has provided better outcomes against CD20+ B-cell lymphomas than chemotherapy with conventional antitumor drugs alone. Treatment with rituximab poses a considerable problem, however, because of CD20- tumor transformation and subsequent disease progression. We have established a CD20- lymphoma cell line, RRBL1, from a diffuse large B-cell lymphoma with CD20- transformation from CD20+ follicular lymphoma after treatment with rituximab. RRBL1 was CD10+, CD19+, and CD20- by flow cytometry. CD20 expression was not detected by immunohistochemistry. Immunoblotting with whole RRBL1 cell lysate showed a very faint CD20 band only with longer exposures. The level of CD20 messenger RNA (mRNA) expression detected by quantitative reverse transcriptase-polymerase chain reaction analysis was almost 100 times lower than that in CD20+ lymphoma cells. When we treated RRBL1 cells with trichostatin A, an epigenetic drug that modulates histone-acetylation status, we detected dramatically increased CD20 mRNA and protein expression, suggesting that epigenetic mechanisms may explain the CD20- phenotype in RRBL1 cells. Thus, RRBL1 may be useful not only for analyses of mechanisms for the absence of CD20 expression in vitro but also for exploration of therapies against CD20- B-cell malignancies in vivo.
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PMID:Epigenetic regulation of CD20 protein expression in a novel B-cell lymphoma cell line, RRBL1, established from a patient treated repeatedly with rituximab-containing chemotherapy. 1767 67

The improvement of the transfection efficiency of the non-viral-based gene delivery systems is a key issue for the application in gene therapy. We have previously described an archaeal histone-like protein-based (HPhA) gene delivery system and showed that HPhA formed stable non-covalent complexes with nucleic acids and improved their delivery by using beta-galactosidase as a reporter gene. In this study, the wild-type p53 gene was transfected into the cancer cells using the HPhA as a vector, and the expression level and the activity of p53 gene were evaluated both in vitro and in vivo. Gene expression was determined by real-time reverse transcriptase-PCR and western blotting analysis. The cellular growth inhibition and apoptosis of HPhA-mediated p53 transfection were assessed by XTT (sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)benzene sulfonic acid hydrate) assay and annexin V-FITC (fluorescein isothiocyanate) staining, respectively. Further more, transfection of HPhA/p53 into CNE (nasopharyngeal carcinoma cell line)-xenografted nude mice was performed and tumor growth was measured. The present study demonstrates that HPhA enhances the efficiency of p53 gene transfer and antitumor activity compared with the widely used Lipofectamine. These results demonstrate that HPhA enhances the in vitro and in vivo efficiency of p53 gene transfer and suggest that it may be served as a promising tool for gene delivery and gene therapy.
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PMID:An archaeal histone-like protein mediates efficient p53 gene transfer and facilitates its anti-cancer effect in vitro and in vivo. 1785 24

The impact of vitrification procedures on in vitro matured (IVM) ovine oocytes mRNA content and ability to undergo successful fertilization, cleavage and embronic development was assessed. Vitrified-warmed (n = 113) and control (n = 140) IVM oocytes were in vitro fertilized and cultured up to blastocyst stage under standard conditions. Vitrified oocytes showed lower cleavage rate (47% vs. 75%, P < 0.001) and development to blastocyst stage (17% vs. 57%, P < 0.001) than controls. In addition, the timings of the first cleavage and blastocysts production were significantly delayed in the vitrified-warmed group (P < 0.001 in both cases). In parallel, we analyzed by reverse transcriptase real-time PCR the relative abundance of beta-actin, H2A.Z histone, Poli A Polimerase (PAP), Heat Shock Protein 90 beta (HSP90 beta), P34(cdc2), Cyclin b, Na/K-ATPase and Type I cadherin (E-Cad) transcripts in single IVM controls (n = 24) and vitrified-warmed oocytes (n = 40). Results were normalized against the exogenous rabbit alpha-globin mRNA standard and the beta-actin housekeeping gene and similarly described a lower abundance of most mRNAs in oocytes subjected to vitrification procedures. When normalized against the exogenous standard mRNA, all transcripts except for beta-actin and H2A.Z showed a significantly different abundance in the two classes of oocytes. The same results were obtained after normalization against the internal standard, except for HSP90 beta and E-Cad transcripts, whose lower abundance in vitrified-warmed oocytes resulted prominent, but not significant (P = 0.083 and P = 0.068, respectively). The oocyte lower transcripts abundance following vitrification might be an early indicator of poor quality in good correlation with the developmental data to blastocyst stage.
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PMID:Vitrification of in vitro matured ovine oocytes affects in vitro pre-implantation development and mRNA abundance. 1788 74

Reepithelialization of human suction blister wounds was examined in five normal human volunteers over a period of 14 days postwounding to understand the control of keratinocyte migration, proliferation, and differentiation in acute wound healing in a controlled model. The hypothesis that morphological changes and progenitor activation result from altered cytokines and growth factor expression [in particular interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), transforming growth factor alpha (TGF-alpha), TGF-beta 1, and keratinocyte growth factor] was tested using semiquantitative immunohistochemistry combined with reverse transcriptase-polymerase chain reaction of samples from the blister roof, edge, and base. Parallel changes in keratin expression were examined using a wide range of well-established antibodies to multiple keratins and in situ hybridization for keratin 16 (K16), a marker of the hyperproliferative (mucoregenerative) phenotype. Longitudinal morphological, semiquantitative cytokine and growth factor expression, and histometric histone and cytokeratin profiles suggest three phases to reepithelialization: phase 1, or the acute activation phase, early in the first 24 hours postwounding is characterized by epidermal expression of IL-1beta and IL-6, and dermal expression of TGF-beta1, as basal, upper outer root sheath, and putative interfollicular transit amplifying keratinocytes become committed to mitosis; phase 2, or the early activation phase, late in the second 24 hours postwounding, characterized by epidermal expression of TGF-alpha and IL-6 with concurrent suprabasal K16 expression and migration with continued proliferation, and dermal expression of keratinocyte growth factor and IL-6; and phase 3 or restitution over the following 2 weeks, characterized by the return of normal homeostasis, including bulge activation as evidenced by K19 expression.
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PMID:Epidermal repair results from activation of follicular and epidermal progenitor keratinocytes mediated by a growth factor cascade. 1797 Oct 15


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