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

Prostate cells present in the peripheral circulation can be detected using an enhanced reverse-transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) assay. In one study, preoperative enhanced RT-PCR for PSA status was a significant predictor of surgical pathology and postoperative biomechanical recurrence. The use of RT-PCR may enhance the urologist's ability to stage potential candidates for radical prostatectomy, as the assay is a more sensitive and specific predictor of microscopic extracapsular extension than conventional staging modalities. This highly adaptable assay also may have roles in screening for recurrence and in staging other solid tumors.
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PMID:The role of the reverse-transcriptase polymerase chain reaction assay for prostate-specific antigen in the selection of patients for radical prostatectomy. 894 9

We analyzed complexed and free prostate-specific antigen (PSA), the free/total PSA and complexed/free PSA ratios, acid phosphatase, and prostatic phosphatase in serum from 36 patients with prostatic carcinoma and from 48 non-neoplastic control patients (20 with prostatitis and 28 with benign prostatic hyperplasia). Receiver-operating characteristic plots showed that serum PSA was the most efficient variable, singly used, in discriminating neoplastic from non-neoplastic patients. At a cut-off value of 10.0 ng/ml, serum PSA had a diagnostic sensitivity of 87% and a diagnostic specificity of 83%. In particular, three patients with prostatic carcinoma and twenty non-neoplastic controls had serum PSA levels of between 4 and 10 ng/ml. The subsequent analysis of the serum free/total PSA ratio, in this subgroup, using a cut-off level of 15%, allowed us to classify correctly all prostatic cancer cases and 18/20 non-neoplastic diseases. We next analyzed PSA mRNA in circulating cells using an improved reverse-transcriptase polymerase chain reaction dot blot procedure, from six patients with prostatic carcinoma with distant metastases, and in seventeen with localized cancer. The analysis had a high sensitivity (up to dilutions 1:10(6) of total RNA from prostatic cancer cells vs total RNA from normal blood cells). The analysis revealed circulating micrometastatic cells in 3/6 (50%) cases of metastatic cancer and in 4/17 cases of localized cancer. To conclude, serum total PSA combined with the free/total PSA ratio is a very efficient algorithm in discriminating neoplastic from non-neoplastic prostatic diseases, while other mRNA species must be analyzed, in addition to PSA mRNA, in circulating cells to increase the efficiency in detecting metastatic prostatic cancer.
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PMID:Prostate-specific antigen (protein and mRNA) analysis in the differential diagnosis and staging of prostate cancer. 935 30

Reverse transcriptase polymerase chain reaction (RT-PCR) assay is a sensitive technique to detect circulating cells expressing prostate-specific antigen (PSA) in blood or bone marrow from patients with prostate cancer. When applied to prostate cancer patients at our institution, this technique identifies those patients with a greater likelihood of extra-prostatic disease. We evaluated RT-PCR PSA as a predictor of PSA recurrence and compared it with pre-operative (serum PSA, digital rectal examination, Gleason score on biopsy) and post-operative parameters (pathological findings). Three hundred nineteen men scheduled for radical prostatectomy had an enhanced RT-PCR PSA assay before surgery. The enhanced RT-PCR PSA protocol has been previously described. PSA recurrence was defined as any serum PSA value above 0.2 microgram/l. Forty-six patients had PSA recurrence. The mean follow-up was 25.4 months. Recurrence free survival was 53% for patients with positive RT-PCR PSA vs. 84% if RT-PCR PSA was negative. By using multivariate analyses, RT-PCR PSA status was not an independent predictor of PSA recurrence compared to pathological stage pT3, Gleason score on prostate specimen and serum PSA. If only pre-operative parameters were studied, serum PSA and RT-PCR PSA status were 2 independent pre-operative predictors of PSA recurrence compared with Gleason score on biopsy and digital rectal examination. Int. J. Cancer (Pred. Oncol.) 84:360-364, 1999.
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PMID:Blood-based reverse transcriptase polymerase chain reaction assays for prostatic specific antigen: long term follow-up confirms the potential utility of this assay in identifying patients more likely to have biochemical recurrence (rising PSA) following radical prostatectomy. 1040 86

Reverse transcriptase-polymerase chain reaction (RT-PCR) assay for prostate-specific antigen and immunocytochemistry for cytokeratin-18 (CK-18) are tests for the detection of microdisseminated carcinoma of the prostate. Bone marrow aspirates and peripheral venous blood from 50 patients with clinically organ-confined prostate cancer were examined. The rate of positive results was independent of the pT stage, serum PSA, and previous antiandrogen treatment. RT-PCR and immunocytochemistry have to be tested under standardized conditions in prospective trials, and the results have to be compared to the serum PSA follow-up.
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PMID:[Reverse transcriptase polymerase chain reaction and immunocytochemistry of bone marrow aspiration specimen and peripheral blood for detection of microdisseminated prostatic carcinoma. A comparative analysis]. 1121 48

Androgen receptor (AR) may communicate with the general transcription machinery on the core promoter to exert its function as a transcriptional modulator. Our previous report demonstrated that the AR interacted with transcription factor IIH (TFIIH) under physiological conditions and that overexpression of Cdk-activating kinase, the kinase moiety of TFIIH, enhanced AR-mediated transcription in prostate cancer cells. In an effort to further dissect the mechanisms implicated in AR transactivation, we report here that AR interacts with PITALRE, a kinase subunit of positive elongation factor b (P-TEFb). Cotransfection of the plasmid encoding the mutant PITALRE (mtPITALRE), defective in its RNA polymerase II COOH-terminal domain (CTD)-kinase activity, resulted in preferential inhibition of AR-mediated transactivation. Indeed, AR transactivation in PC-3 cells was preferentially inhibited at the low concentration of 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB), a CTD kinase inhibitor. These results suggest that CTD phosphorylation may play an important role in AR-mediated transcription. Furthermore, a nuclear run-on transcription assay of the prostate-specific antigen gene, an androgen-inducible gene, showed that transcription efficiency of the distal region of the gene was enhanced upon androgen induction. Taken together, our reports suggest that AR interacts with TFIIH and P-TEFb and enhances the elongation stage of transcription.
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PMID:Androgen receptor interacts with the positive elongation factor P-TEFb and enhances the efficiency of transcriptional elongation. 1126 37

We have used the chromatin immunoprecipitation technique to analyze the formation of the androgen receptor (AR) transcription complex onto prostate-specific antigen (PSA) and kallikrein 2 promoters in LNCaP cells. Our results show that loading of holo-AR and recruitment of RNA polymerase II to the promoters occur transiently. The cyclic nature of AR transcription complex assembly is also illustrated by transient association of coactivators GRIP1 and CREB-binding protein and acetylated histone H3 with the PSA promoter. Treatment of cells with the pure antiandrogen bicalutamide also elicits occupancy of the promoter by AR. In contrast to the agonist-liganded AR, bicalutamide-bound receptor is not capable of recruiting polymerase II, GRIP1, or CREB-binding protein, indicating that the conformation of AR bound to anti-androgen is not competent to assemble transcription complexes. Proteasome is involved in the regulation of AR-dependent transcription, as a proteasome inhibitor, MG-132, prevents the release of the receptor from the PSA promoter, and it also blocks the androgen-induced PSA mRNA accumulation. Furthermore, occupancy of the PSA promoter by the 19 S proteasome subcomplex parallels that by AR. Collectively, formation of the AR transcription complex, encompassing AR, polymerase II, and coactivators, on a regulated promoter is a cyclic process involving proteasome function.
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PMID:Involvement of proteasome in the dynamic assembly of the androgen receptor transcription complex. 1237 34

The androgen receptor, like other nuclear receptors, activates target genes by binding to hormone-responsive enhancers. Here we demonstrate that androgen induces robust recruitment of androgen receptor, members of the p160 coactivator family, and CREB-binding protein p300 specifically at the distant enhancer of prostate-specific antigen (PSA) gene. Unexpectedly, we found that RNA polymerase II (Pol II) is directly recruited to the enhancer in a hormone-dependent manner, independent of the proximal promoter, and that the isolated PSA enhancer can mediate efficient androgen induction of transcription. Inhibition of the Pol II carboxyl-terminal domain kinase activity with low concentrations of flavopiridol blocks Pol II transfer from the enhancer to the promoter and selectively abolishes PSA induction by androgen. Moreover, elevated levels of the p160 coactivator ACTR/AIB1 increase both androgen-dependent and -independent PSA expression, by facilitating Pol II recruitment to the enhancer. These results support a model in which nuclear receptors and their coactivators mediate hormone induction by serving as a staging platform for Pol II recruitment.
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PMID:Androgen-induced recruitment of RNA polymerase II to a nuclear receptor-p160 coactivator complex. 1258 22

The early androgen-dependent (AD) phase of prostate cancer is dependent on the androgen receptor (AR). However, it is unclear whether AR is fully functional in recurrent prostate cancer after androgen withdrawal. To address this issue we interrogated AR signaling in AD and recurrent prostate cancer xenografts using molecular imaging, chromatin immunoprecipitation, and immunohistochemistry. In the imaging experiments, an adenovirus bearing a two-step transcriptional activation cassette, which amplifies AR-dependent firefly luciferase reporter gene activity, was injected into tumors implanted into severe combined immunodeficiency mice. A charge-coupled device optical imaging system detected the initial loss and then resumption of AR transcriptional activity in D-luciferin-injected mice as tumors transitioned from AD to recurrent growth. The results of chromatin immunoprecipitation and immunohistochemical localization experiments correlated with the Ad two-step transcriptional activation imaging signal. AR localized to the nucleus and bound to the endogenous prostate-specific antigen enhancer in AD tumors but exited the nucleus and dissociated from the enhancer upon castration. However, AR reentered the nucleus and rebound the prostate-specific antigen enhancer as the cancer transitioned into the recurrent phase. Surprisingly, RNA polymerase II and the general factor TFIIB remained bound to the gene throughout the transition. Our data support the concept that AR is fully functional in recurrent cancer and suggest a model by which a poised but largely inactive transcription complex facilitates reactivation by AR at castrate levels of ligand.
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PMID:Interrogating androgen receptor function in recurrent prostate cancer. 1290 31

We have used chromatin immunoprecipitation (ChIP) assay to follow transcription factor loading and monitor changes in covalent histone modifications associated with the prostate-specific antigen and kallikrein (KLK2) genes in response to androgen and antiandrogen in LNCaP cells. The dynamics of testosterone (T)-induced loading of androgen receptor (AR) onto the proximal promoters of the genes differed significantly from that onto the distal enhancers. Significantly more holo-AR was loaded onto the enhancers than the promoters, but the receptor's residence time was more transient on the enhancers. Even though holo-AR recruited some RNA polymerase II (Pol II) onto the enhancers, the principal Pol II transcription complex was assembled on the promoters. The pure antiandrogen bicalutamide (CDX) complexed to AR elicited occupancy of the prostate-specific antigen promoter, but not that of the enhancer, whereas the partial antagonists cyproterone acetate (CPA) and mifepristone (RU486) were capable of promoting AR loading also onto the enhancer. In contrast to the CDX-occupied receptor, both CPA- and RU486-bound AR recruited Pol II and coactivators p300 and glucocorticoid receptor-interacting protein 1 (GRIP1) onto the promoter and enhancer. However, CPA and RU486 also brought about a simultaneous recruitment of the nuclear receptor corepressor (NCOR) onto the promoter as efficiently as CDX. There were dynamic changes in covalent modifications of histone H3: acetylation of lysine 9 and 14, methylation of arginine 17, phosphorylation of serine 10 as well as di- and tri-methylation at lysine 4 of the H3 N-terminal tail were enhanced in response to T, but not after CDX treatment. Collectively, these results indicate that transcriptional activation by AR is accompanied by a cascade of distinct covalent histone modifications and that the pure antiandrogen CDX and the partial antagonists CPA and RU486 exhibit clear differences in their ability to promote recruitment of histone-acetylating and histone-deacetylating complexes in human prostate cancer cells.
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PMID:Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor. 1530 89

The success of gene therapy using a RNA interference approach relies on small interfering RNA (siRNA) expression from a highly tissue-specific RNA polymerase II promoter rather than from ubiquitous RNA polymerase III. Accordingly, we have developed a prostate-specific vector that expresses siRNAs from the human prostate-specific antigen promoter, a RNA polymerase II promoter. Our data demonstrate androgen-dependent and tissue-specific siRNA-mediated gene silencing in the androgen-responsive prostate cancer cell line, LNCaP. The biological significance was evidenced by altered apoptotic activity through the inhibition of the apoptosis-related regulatory gene. These results demonstrate that siRNA-mediated gene silencing from a tissue-specific RNA polymerase II promoter could be a potential tool for tissue-specific gene therapy.
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PMID:Gene silencing in androgen-responsive prostate cancer cells from the tissue-specific prostate-specific antigen promoter. 1552 Jan 64


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