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

---

Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cdc kinase subunit 1 (Cks1) has been shown to involve in the regulation of cell cycle progression and p27Kip1 degradation. To define the role of Cks1 in lung tumorigenesis, we examined the expression of Cks1 in human lung cancer cell lines and tested the effect of Cks1-specific small interfering RNA (siRNA) on these cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis showed that Cks1 was highly expressed in human lung cancer cells. Transfection of Cks1 siRNA down-regulated Cdc2 kinase activity and induced G2/M arrest in Cks1- overexpressing H358 lung cancer cells. Long-term treatment of Cks1 siRNA induced caspase activation and apoptosis in H358 cells. On the contrary, Cks1 siRNA did not affect viability of normal human lung fibroblasts under the same experimental condition. Collectively, our results suggest that Cks1 participates in the steps of lung tumorigenesis and this gene may be a target for the treatment of lung cancer.
...
PMID:RNA silencing of Cks1 induced G2/M arrest and apoptosis in human lung cancer cells. 1611 16

A number of methods exist to detect levels of telomerase activity and the presence of telomerase subunits in a variety of tissues. As telomerase activation seems to be an important step in tumorigenesis, accurate detection of the presence and activity of the enzyme and its subunits is vital. The original method of detecting telomerase activity was developed by Kim and coworkers in 1994, and was termed the telomeric repeat amplification protocol. This assay led to a staggering increase in the number of telomerase-associated publications in scientific journals (85 publications from 1974-1994, 5063 publications from 1994-2004). A number of methods have been described to detect telomeres and to measure their length, with the standard measurement of telomere length performed using a modification of the Southern blot protocol. RNA in situ hybridization can be performed to detect levels of the RNA component of telomerase, and standard in situ hybridization and immunohistochemistry can be applied to examine expression levels and localization of the catalytic subunit of the enzyme. Reverse transcriptase PCR has also been applied to assess expression levels of the telomerase components in various tissues. This review provides a synopsis of telomeres, telomerase, telomerase and cancer, and finally, methods for the detection of telomerase in cancer.
...
PMID:Telomerase: is it the future diagnostic and prognostic tool in human cancer? 1625 32

Hypoxia inducible factor (HIF), a master regulator of critical genes for cell survival under hypoxic conditions, is known to be related to tumorigenesis and progression of renal cell carcinoma. N-methylpyrrole (Py)-N-methylimidazole (Im) hairpin polyamides are synthetic organic compounds that recognize and bind to the minor grooves of specific DNA sequences. We synthesized three Py-Im hairpin polyamides targeting the flanking sequences of hypoxia responsive element (HRE; a binding site of HIF) in the promoter region of the vascular endothelial growth factor (VEGF) gene. The effects of the polyamides on HIF-induced transcription were evaluated by a luciferase assay using a reporter plasmid containing a VEGF promoter. Real time reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay were performed to examine the effects of the polyamides on the transcription and secretion of VEGF in A498 renal cell carcinoma cells, which have a frame-shift mutation in the von Hippel-Lindau gene. A combination of three Py-Im hairpin polyamides suppressed HIF-induced transcription in reporter assays using 293 cells and successfully suppressed transcription and translation of the VEGF gene in A498 cells. Inhibition of the HIF-HRE interaction was confirmed by an electrophoresis mobility shift assay. An approach using Py-Im hairpin polyamides may be a new strategy for the treatment of renal cell carcinoma.
...
PMID:Suppression of VEGF transcription in renal cell carcinoma cells by pyrrole-imidazole hairpin polyamides targeting the hypoxia responsive element. 1664 75

Very few of the genes that are important in pituitary tumor initiation, progression, and metastasis have been identified to date. To identify potential genes that may be important in pituitary tumor progression and carcinoma development, we used Affymetrix GeneChip HGU-133A-oligonucleotide arrays, which contain more than 15,000 characterized genes from the human genome to study gene expression in an ACTH pituitary carcinoma metastatic to the liver and four pituitary adenomas. Reverse-transcriptase real-time quantitative- PCR (RT-qPCR) was then used to analyze 4 nonneoplastic pituitaries, 19 adenomas, and the ACTH carcinoma. A larger series of pituitary adenomas and carcinomas were also analyzed for protein expression using tissue microarrays (TMA) (n = 233) and by Western blotting (n = 18). There were 4298 genes that were differentially expressed among the adenomas compared to the carcinoma, with 2057 genes overexpressed and 2241 genes underexpressed in the adenomas. The beta-galactoside binding protein galactin-3 was underexpressed in some adenomas compared to the carcinomas. Prolactin (PRL) and ACTH tumors had the highest levels of expression of galectin-3. The human achaetescute homolog-1 ASCL1 (hASH-1) gene was also underexpressed in some adenomas compared to the carcinoma. Prolactin and ACTH tumors had the highest levels of expression of hASH-1. ID2, which has an important role in cell development and tumorigenesis, was underexpressed in some adenomas compared to the carcinomas. Transducin-like enhancer of split four/ Groucho (TLE-4) was over-expressed in adenomas compared to the ACTH carcinoma. The differential expression of these genes was validated by RT-qPCR, by immunohistochemistry using TMA and by Western blotting. These results indicate that the LGALS3, hASH1, ID2, and TLE-4 genes may have important roles in the development of pituitary carcinomas.
...
PMID:Patterns of gene expression in pituitary carcinomas and adenomas analyzed by high-density oligonucleotide arrays, reverse transcriptase-quantitative PCR, and protein expression. 1694 82

The EBER genes of Epstein-Barr virus (EBV) are transcribed by RNA polymerase (pol) III to produce untranslated RNAs that are implicated in oncogenesis. These EBER transcripts are the most highly expressed viral gene products in EBV-transformed cells. We have identified changes to the cellular transcription machinery that may contribute to the high levels of EBER RNA. These include phosphorylation of ATF2, which interacts with EBER promoters. A second is induction of TFIIIC, a pol III-specific factor that activates EBER genes; all five subunits of TFIIIC are overexpressed in EBV-positive cells. In addition, EBV induces BDP1, a subunit of the pol III-specific factor TFIIIB. Although BDP1 is the only TFIIIB subunit induced by EBV, its induction is sufficient to stimulate EBER expression in vivo, implying a limiting function. The elevated levels of BDP1 and TFIIIC in EBV-positive cells stimulate production of tRNA, 7SL, and 5S rRNA. Abnormally high expression of these cellular pol III products may contribute to the ability of EBV to enhance growth potential.
...
PMID:Epstein-Barr virus induces cellular transcription factors to allow active expression of EBER genes by RNA polymerase III. 1695 91

The product of the von Hippel-Lindau gene (VHL) acts as the substrate-recognition component of an E3 ubiquitin ligase complex that ubiquitylates the catalytic alpha subunit of hypoxia-inducible factor (HIF) for oxygen-dependent destruction. Although emerging evidence supports the notion that deregulated accumulation of HIF upon the loss of VHL is crucial for the development of clear-cell renal cell carcinoma (CC-RCC), the molecular events downstream of HIF governing renal oncogenesis remain unclear. Here, we show that the expression of a homophilic adhesion molecule, E-cadherin, a major constituent of epithelial cell junctions whose loss is associated with the progression of epithelial cancers, is significantly down-regulated in primary CC-RCC and CC-RCC cell lines devoid of VHL. Reintroduction of wild-type VHL in CC-RCC (VHL(-/-)) cells markedly reduced the expression of E2 box-dependent E-cadherin-specific transcriptional repressors Snail and SIP1 and concomitantly restored E-cadherin expression. RNA interference-mediated knockdown of HIFalpha in CC-RCC (VHL(-/-)) cells likewise increased E-cadherin expression, while functional hypoxia or expression of VHL mutants incapable of promoting HIFalpha degradation attenuated E-cadherin expression, correlating with the disengagement of RNA polymerase II from the endogenous E-cadherin promoter/gene. These findings reveal a critical HIF-dependent molecular pathway connecting VHL, an established "gatekeeper" of the renal epithelium, with a major epithelial tumor suppressor, E-cadherin.
...
PMID:VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail. 1706 Apr 62

Polyamine analogs are known to inhibit tumorigenesis at least in part by mimicking some of the regulatory roles of natural polyamines. To begin the identification of those signaling pathways that are involved in differential cellular responses to the synthetic conformationally restricted polyamine analog CGC-11093, we conducted gene expression profiling, proteomic, and genome-wide DNA methylation and histone acetylation analyses of the HCT116 colon adenocarcinoma cell line after treatment with this analog. Gene expression analysis was performed using Affymetrix GeneChip human genome U133 Plus 2.0 arrays. Changes in protein expression were evaluated using 2D polyacrylamide gels followed by LCMS/MS. DNA methylation was measured using 6,800 element CpG island microarrays. Treatment of cells with CGC-11093 at concentrations ranging from 0.1 to 10 microM caused inhibition of cell growth and metabolic activity, but only minimally affected cell viability. Gene expression analysis showed concentration-dependent effects of CGC-11093 on the DNA/RNA binding transcription factor, cell cycle, signaling, transport, cytoskeletal/structural, and serine protease genes. Functional gene analysis revealed distinct expression patterns related to inhibition of cell cycle control, TGF beta signaling, proteasome and RNA polymerase pathways, upregulation of the aminoacyl-tRNA synthesis pathway, and perturbations in the MAPK and Wnt signaling pathways. Microarray results were validated for selected genes with real time RT PCR. Proteomics analysis showed correlative changes in the expression of proteins involved in the regulation of proteasome function (proteasome subunit Y) and tRNA synthesis. CGC-11093 treatment did not produce any detectable changes in DNA methylation or histone acetylation in cells. This study validates specific target pathways for a specific conformationally restricted polyamine analog and suggests the utility of combined gene and DNA methylation microarrays along with proteomic analyses as a useful approach to the evaluation of the mechanisms of action of anticancer drugs.
...
PMID:Pharmacogenomics of the polyamine analog 3,8,13,18-tetraaza-10,11-[(E)-1,2-cyclopropyl]eicosane tetrahydrochloride, CGC-11093, in the colon adenocarcinoma cell line HCT1161. 1712 31

Transformed cells express high levels of non-telomeric reverse-transcriptase (RT) activity of retrotransposon and endogenous retrovirus origin. We previously reported that RT inhibition, either pharmacological or through transient silencing of RT-encoding LINE-1 (L1) elements by RNA interference (RNAi), reduced proliferation, induced differentiation and reprogrammed gene expression in human tumorigenic cell lines. Moreover, the antiretroviral drug efavirenz antagonized tumor progression in animal models in vivo. To get insight into the role of retroelements in tumorigenesis, we have now produced two cell lines derived from A-375 melanoma, in which the expression of either L1 retrotransposon, or HERV-K endogenous retrovirus, was stably suppressed by RNAi. Compared to the parental A-375 cell line, cells with stably interfered L1 expression show a lower proliferation rate, a differentiated morphology and lower tumorigenicity when inoculated in nude mice. L1 silencing modulates expression of several genes and, unexpectedly, also downregulates HERV-K expression. In HERV-K interfered cells, instead, L1 expression was unaffected, and cell proliferation and differentiation remained unchanged compared to parental A-375 cells. In vivo, however, their tumorigenic potential was found to be reduced after inoculation in nude mice. These results suggest that L1 and HERV-K play specific and distinct roles in cell transformation and tumor progression.
...
PMID:Distinct roles for LINE-1 and HERV-K retroelements in cell proliferation, differentiation and tumor progression. 1723 20

Genetic instabilities are believed to be one of the major causes of developing a cancer phenotype in humans. During the progression of cancer, aberrant expression of proteins, either owing to genetic (amplification, mutation and deletion) or epigenetic modifications (DNA methylation and histone deacetylation), contributes in different ways to the development of cancer. By differential screening analysis, an amplification of the 19q13 locus containing a novel pancreatic differentiation 2 (PD2) gene was identified. PD2 is the human homolog of the yeast RNA polymerase II-associated factor 1 (yPaf1) and is part of the human RNA polymerase II-associated factor (hPAF) complex. hPAF is comprised of five subunits that include PD2/hPaf1, parafibromin, hLeo1, hCtr9 and hSki8. This multifaceted complex was first identified in yeast (yPAF) and subsequently in Drosophila and human. Recent advances in the study on PAF have revealed various functions of the complex in human, which are similar to yPAF, including efficient transcription elongation, mRNA quality control and cell-cycle regulation. Although the precise function of this complex in cancer is not clearly known, some of its subunits have been linked to a malignant phenotype. Its core subunit, PD2/hPaf1, is amplified and overexpressed in many cancers. Further, an overexpression of PD2/hPaf1 results in the induction of a transformed phenotype, suggesting its possible involvement in tumorigenesis. The parafibromin subunit of the hPAF complex is a product of the HRPT-2 (hereditary hyperparathyroidism type 2) tumor suppressor gene, which is mutated in the germ line of hyperparathyroidism-jaw tumor patients. This review focuses on the functions of the PAF complex and its individual subunits, the interaction of the subunits with each other and/or with other molecules, and dysregulation of the complex, providing an insight into its potential involvement in the development of cancer.
...
PMID:Human RNA polymerase II-associated factor complex: dysregulation in cancer. 1759 57

Transcription in eukaryotes is a tightly regulated, multistep process. Gene-specific transcriptional activators, several different co-activators and general transcription factors are necessary to access specific loci to allow precise initiation of RNA polymerase II transcription. As the dense chromatin folding of the genome does not allow the access of these sites by the huge multiprotein transcription machinery, remodelling is required to loosen up the chromatin structure for successful transcription initiation. In the present review, we summarize the recent evolution of our understanding of the function of two histone acetyl transferases (ATs) from metazoan organisms: GCN5 and PCAF. Their overall structure and the multiprotein complexes in which they are carrying out their activities are discussed. Metazoan GCN5 and PCAF are subunits of at least two types of multiprotein complexes, one having a molecular weight of 2 MDa (SPT3-TAF9-GCN5 acetyl transferase/TATA binding protein (TBP)-free-TAF complex/PCAF complexes) and a second type with about a size of 700 kDa (ATAC complex). These complexes possess global histone acetylation activity and locus-specific co-activator functions together with AT activity on non-histone substrates. Thus, their biological functions cover a wide range of tasks and render them indispensable for the normal function of cells. That deregulation of the global and/or specific AT activities of these complexes leads to the cancerous transformation of the cells highlights their importance in cellular processes. The possible effects of GCN5 and PCAF in tumorigenesis are also discussed.
...
PMID:Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation. 1769 77


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---