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)

Information on over- and underexpressed genes in prostate cancer in comparison to adjacent normal tissue was sought by DNA microarray analysis. Approximately 12,600 mRNA sequences were analyzed from a total of 26 tissue samples (17 untreated prostate cancers, 9 normal adjacent to prostate cancer tissues) obtained by prostatectomy. Hierarchical clustering was performed. Expression levels of 63 genes were found significantly (at least 2.5-fold) increased, whereas expression of 153 genes was decreased (at least 2.5-fold) in prostate cancer versus adjacent normal tissue. In addition to previously described genes such as hepsin, overexpression of several genes was found that has not drawn attention before, such as the genes encoding the specific granule protein (SGP28), alpha-methyl-acyl-CoA racemase, low density lipoprotein (LDL)-phospholipase A2, and the anti-apoptotic gene PYCR1. The radiosensitivity gene ATDC and the genes encoding the DNA-binding protein inhibitor ID1 and the phospholipase inhibitor uteroglobin were significantly down-regulated in the cancer samples. DNA microarray data for eight genes were confirmed quantitatively in five normal and five cancer tissues by real-time reverse transcriptase-polymerase chain reaction with a high correlation between the two methods. Laser capture microdissection of epithelial and stromal compartments from cancer and histological normal specimens followed by an amplification protocol for low levels of RNA (<0.1 microg) allowed us to distinguish between gene expression profiles characteristic of epithelial cells and those typical of stroma. Most of the genes identified in the nonmicrodissected tumor material as up-regulated were indeed overexpressed in cancerous epithelium rather than in the stromal compartment. We conclude that development of prostate cancer is associated with down-regulation as well as up-regulation of genes that show complex differential regulation in epithelia and stroma. Some of the gene expression alterations identified in this study may prove useful in the development of novel diagnostic and therapeutic strategies.
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PMID:Decrease and gain of gene expression are equally discriminatory markers for prostate carcinoma: a gene expression analysis on total and microdissected prostate tissue. 1205 20

The objective of this study was to study the expression of estrogen receptor-beta (ER-beta) in prostatic adenocarcinoma and correlate it with Gleason grade and clinical outcome. Immunohistochemical evaluation was performed on prostate needle biopsies from 53 patients (T1-T3pN0M0). ER-beta and ER-alpha transcripts were also studied by semiquantitative reverse transcriptase polymerase chain reaction in PC-3 and LNCaP prostate carcinoma cell lines. ERbeta was expressed in 93% of adenocarcinomas and was positively associated with primary Gleason grade (P = 0.028 for percentage of positive cells and P = 0.046 using a semiquantitative scale) and Gleason score (P = 0.010 for percentage of positive cells and P = 0.014 using a semiquantitative scale). ER-beta expression in the benign epithelium of prostates with adenocarcinoma was detected in 92% of cases and in the stroma in 47% of cases. A trend for longer time to treatment failure was noted for cases with low ER-beta expression after curatively intended radiotherapy (P = 0.082). PC-3, an aggressive prostate cancer cell line with invasive properties in nude mice, expressed higher levels of ER-beta than LNCaP, a nonmetastasizing cell line, whereas no difference for ER-alpha transcripts could be observed. Our findings suggest that ER-beta, as detected by PPG5/10 antibody, may have a role in the process of dedifferentiation of prostate adenocarcinomas, with higher levels present in less differentiated tumors.
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PMID:Prostate carcinoma expression of estrogen receptor-beta as detected by PPG5/10 antibody has positive association with primary Gleason grade and Gleason score. 1215 65

We have cloned a cDNA coding for a novel steroid receptor co-activator protein termed SRAP from a rat prostate library. Although the nucleotide sequence of the SRAP has 78.2% identity to that of the human steroid receptor RNA activator (SRA), a novel RNA molecule which was reported to act as an RNA transcript without being translated into protein [Lanz, McKenna, Onate, Albrecht, Wong, Tsai, Tsai and O'Malley (1999) Cell 97, 17-27], the cDNA of SRAP is capable of generating a functional protein. Glutathione S-transferase pull-down assays showed that SRAP associates with the partial androgen receptor (AR) protein composed of a DNA-binding domain and an activation function 2. Luciferase assays demonstrated that SRAP enhances the transactivation activity of the AR, the glucocorticoid receptor and the peroxisome proliferator-activated receptor gamma(1) in a ligand-dependent manner. Using a green fluorescent protein (GFP) fusion-protein construct, we demonstrated in vivo translation of the GFP-SRAP fusion protein in HeLa cells co-transfected with pSG5AR and reporter gene in the presence of 5 alpha-dihydrotestosterone (DHT). Co-transfection of the GFP-SRAP fusion protein expression plasmid enhanced the transactivation activity of AR whereas incorporation of mutations in SRAP of the fusion protein resulted in loss of enhancement of the transactivation activity. Northern blot analysis and reverse transcriptase PCR assays showed that SRAP and SRA are expressed in rat and human prostate cancer cell lines respectively. In HeLa cells and the human prostate cancer cells line DU-145, co-transfected with SRAP, the DHT-dependent transactivation activities of AR were not completely inhibited by the anti-androgen flutamide, but the transactivation activities still remained high even in the presence of 5 microM flutamide, suggesting that SRAP may play an important role in enhancing AR activity in prostate cancer.
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PMID:A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity. 1235 Feb 25

Many kallikrein genes were found to be differentially expressed in various malignancies, and prostate specific antigen (encoded by the KLK3 gene) is the best tumour marker for prostate cancer. Prostate specific antigen has recently been shown to be an independent favourable prognostic marker for breast cancer. KLK15 is newly discovered kallikrein gene that is located adjacent to KLK3 on chromosome 19q13.4. KLK15 has 41% similarity to KLK3 and the encoded protein, hK15, can activate pro-prostate specific antigen. We studied the expression of KLK15 by real-time quantitative reverse transcriptase-polymerase chain reaction in 202 tissues from patients with breast carcinoma of various stages, grades and histological types. KLK15 expression was found to be a significant predictor of progression-free survival (hazard ratio of 0.41 and P=0.011) and overall survival (hazard ratio of 0.34 and P=0.009). When all other known confounders were controlled in the multivariate analysis, KLK15 retained its prognostic significance. Higher concentrations of KLK15 mRNA were found more frequently in node negative patients (P=0.042). No association was found between KLK15 expression and any other clinicopathological variable. Further, KLK15 is an independent prognostic factor of progression-free survival and overall survival in the subgroup of patients with lower grade and those with oestrogen receptor and progesterone receptor negative tumours in both univariate and multivariate analysis. KLK15 levels of expression were slightly higher (although not statistically significant) in the oestrogen receptor negative and progesterone receptor negative subgroups of patients. KLK15 is up-regulated by androgens in breast cancer cell lines. Time-course and blocking experiments suggest that this regulation is mediated through the androgen receptor.
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PMID:The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer. 1243 20

African-Americans (AAM) with prostate cancer are more likely to relapse than Caucasian-Americans (CAM) despite controlling for known prognostic factors. One explanation may be that micrometastatic disease in AAM behaves more aggressively than in CAM. We tested this hypothesis by comparing the reverse transcriptase polymerase chain reaction amplification of the Prostatic Specific Antigen-mRNA (RTPCR PSA-mRNA) results from peripheral blood samples of AAM and CAM with respect to disease outcome. We evaluated the peripheral blood of 246 consecutive patients at the time of radical prostatectomy. The RTPCR PSA-mRNA test for determination of circulating prostate cancer cells was performed. The results were stratified by races and correlated with standard clinico-pathological variables and disease free survival. 27% and 23% of AAM and CAM patients were RTPCR PSA-mRNA positive, respectively. The RTPCR PSA-mRNA status correlated with the pathologic stage in CAM but not in AAM, (p = 0.05). There was no association with Gleason score, PSA level, or clinical stage with the RTPCR PSA-mRNA status in either group. AAM with organ-confined prostate cancer were marginally more likely to have circulating prostate cells than similarly staged CAM (24% vs. 17%). In AAM but not CAM who had prostate cancer, the RTPCR PSA-mRNA status correlated with and was an independent predictor of disease-free survival. Our data suggests that, though the likelihood of having circulating prostate cells is the same in AAM and CAM, the presence of circulating prostate cells in AAM is predictive of a worse outcome. This may partially explain the worse prognosis in AAM vs. CAM with clinically localized prostate cancer.
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PMID:Presence of circulating prostate cancer cells in African American males adversely affects survival. 1247 30

Somatostatin (SST) plays an important regulatory role in the physiological control of various organs including the prostate. Somatostatin receptors (SSTRs) and SST analogs are potential targets for prostate cancer treatment, especially since it has been shown that SST analogues are clinically effective in the treatment of advanced prostate cancer. The presence of SST containing neuroendocrine (NE) cells in the epithelium of the human prostate and their suggested role in the paracrine regulation of this gland prompted us to study the potential expression of somatostatin receptors (SSTRs) in human prostatic tissue and prostate cancer cell lines. Using the reverse transcriptase polymerase chain reaction (RT-PCR), we found the SSTR subtypes 1-3 in stromal cells and in prostate cancer cell lines LNCaP, PC-3 and DU 145. Immunohistochemical analysis of 27 radical prostatectomy specimens demonstrated the presence of hSSTR1 in a subpopulation of cancerous and NE cells, whereas hSSTR2 was found in the stroma, peritumoral blood vessels and tumor cells. Receptor subtype 3 was demonstrated to be present on the cell membrane of BPH and malignant areas. A strong immunoreaction (IR) of hSSTR4 was found in tumor cells, as compared with a less intense IR in adjacent BPH areas. Somatostatin receptor subtype 5 was not detectable. Western blot analysis revealed immunoreactive bands of molecular weight between 44-60 kDa. In summary, the present study clearly demonstrates the presence of hSSTR1-3 in tumoral and nontumoral epithelial cells as well as in the stromal compartment, whereas hSSTR4 was found to be confined to epithelial cells, and SSTR5 was not detectable.
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PMID:Localization and mRNA expression of somatostatin receptor subtypes in human prostatic tissue and prostate cancer cell lines. 1247 41

In recent years, the mRNA for prostate-specific antigen (PSA) has been investigated as a potential marker for molecular staging of prostate cancer. We report a simple, rapid, and sensitive assay protocol for the quantification of PSA mRNA in peripheral blood by using reverse transcriptase polymerase chain reaction (RT-PCR) and a chemiluminometric hybridization assay. A recombinant RNA internal standard (IS) that has the same size and primer binding sites as the PSA mRNA is included in the RT-PCR mixture. Total RNA from the sample is coextracted with a constant amount of IS RNA and subjected to RT-PCR. Amplified sequences are labeled with biotin during PCR by using a biotinylated upstream primer. The products are heat-denatured and hybridized with oligonucleotide-specific probes (for PSA and IS) that are immobilized in microtiter wells. Immobilization of oligonucleotide probes is achieved by adsorption of their conjugates with bovine serum albumin. The hybrids are measured using alkaline phosphatase-labeled streptavidin and a dioxetane chemiluminogenic substrate. The ratio of the luminescence values obtained for the PSA mRNA and the RNA IS is a linear function of the initial amount of PSA mRNA present in the sample prior to RT-PCR amplification. The linear range extended from 50 to 500,000 PSA mRNA copies, and the overall reproducibility of the assay, including RT-PCR and hybridization, ranged from 11.5 to 14.2%. Samples containing total RNA from PSA-expressing LNCaP cells give luminescence ratios that are linearly related to the number of cells in the range of 0.04-400 cells. The method was applied to PSA mRNA determination in peripheral blood of healthy individuals, patients with benign prostate hyperplasia, patients with prostate cancer, and patients with other types of localized cancer.
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PMID:Determination of prostate specific antigen mRNA in peripheral blood by reverse transcriptase polymerase chain reaction and a simple chemiluminometric hybridization assay in a high-throughput format. 1257 64

The incidence of prostate cancer is remarkably increased in the last decade. This dramatic epidemiological change can be primarily attributed to the widespread use of prostate specific antigen (PSA) as a diagnostic tool. Nowadays most of the prostate cancers are detected at an early stage and the age of the patients is decreased. This has led to a significantly increase in the number of prostate cancer patients treated by radical prostatectomy. Serum determination of PSA is the standard method to monitor the disease after radical surgery, while other tests can be required only when PSA is detectable. After radical prostatectomy the mean half-life of PSA is 1.5 days and it must become undetectable to consider a patient free of disease. A value greater than 0.4 ng/ml, with an increase in two determination, indicates a recurrence of the disease. PSA is an extremely sensitive marker. In fact, in patients who underwent radical prostatectomy, the presence of detectable serum PSA levels allows to detect tumor recurrence even before any other diagnostic investigation (radiological or scintigraphical) becomes able to document it ("serological" disease). Unfortunately, increasing serum PSA levels do not reveal whether a patient is affected by local relapse or by metastases, with obvious repercussion for the therapeutic choice. Clinical examination of the patient, together with random and echoguided biopsies of the vesico-urethral anastomosis, do not reveal all cases of local recurrence. Ongoing study are evaluating other diagnostic tools in the monitoring patients after radical prostatectomy, such as the serum chromogranin A, the reverse transcriptase-polymerase chain reaction for PSA and prostate specific membrane antigen (PSMA), the Positron Emission Tomography and the immunoscintigraphy with radiolabeled monoclonal antibody directed toward the PSMA.
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PMID:[Clinical surveillance after surgery for prostate cancer]. 1267 77

Gonadotropin-releasing hormone (GnRH) is a neuropeptide that plays a pivotal role in reproductive processes. In recent years, it has become clear that it is also an anti-proliferative agent. GnRH analogs are now used clinically in the treatment of prostate cancer as well as endometriosis and precocious puberty. The target cells of GnRH include the gonadotropes of the anterior pituitary gland and the cells of various hormone-dependent tumors. Only a few target genes have been identified in these cells, however, and little is known concerning their regulation by GnRH. Therefore, we used a quantitative microarray assay to identify the genes that are regulated by GnRH in a murine gonadotrope tumor cell line (LbetaT2). Treatment of LbetaT2 cells with GnRH agonist des-gly(10),[D-Ala(6)]GnRH (GnRHA) for 1 h resulted in alterations in the levels of expression of genes that ranged in magnitude from 1.3- to 159-fold, with a total of 232 genes exhibiting a twofold or greater alteration in expression compared to vehicle treated cells. Of these 232 genes, 149 were up-regulated and, surprisingly, 83 were down-regulated by GnRHA treatment. After 24 h of treatment, the expression of most of the genes that had exhibited altered expression after 1 h of treatment had returned to baseline levels. Moreover, a different profile was observed after 24 h of treatment with 208 genes exhibiting a twofold or greater alteration. Of these, 95 were up-regulated and 113 down-regulated. Most of the affected genes were not known to be responsive to GnRH prior to this study. Treatment with GnRHA was found to affect the expression of a diverse range of genes, including oncogenes and those that encode transcription factors, ion channel proteins, and cytoskeletal proteins as well as other proteins that are involved in signal transduction, the cell cycle, cell proliferation and apoptosis. The altered expression of six of the genes that were found by microarray analysis to be regulated by GnRHA was confirmed by semiquantitative reverse transcriptase-polymerase chain reaction. This is first application of the microarray technique in the study of the global profile of genes regulated by GnRH, and should prove to be a powerful tool for future analysis of the mechanisms by which GnRH regulates the expression of gonadotropins and the growth of tumor cells.
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PMID:Identification of distinct gene expression profiles associated with treatment of LbetaT2 cells with gonadotropin-releasing hormone agonist using microarray analysis. 1271 91

Nitric oxide (NO) is an important signaling molecule for ischemia, inflammation, angiogenesis, immune response, and cell growth and differentiation. It has recently been shown that increased production of NO within various human cancers may contribute to tumor angiogenesis, tumor growth and metastasis, and tumor-related immune suppression. NO can be produced by several NO synthases (NOS), including inducible synthase (iNOS), which is expressed during cell activation and produces NO in larger quantity and for a longer period of time than non-inducible NOSs. In this study, we examined the expression levels of iNOS mRNA and protein in prostate adenocarcinoma using a paired nonneoplastic and neoplastic primary prostate cell culture system and related prostatectomy specimens. Six pairs of neoplastic and nonneoplastic primary prostate cell cultures were established from radical prostatectomy specimens based on homogeneity of the originating tumor and the nonneoplastic tissue. Radioactive reverse transcriptase polymerase chain reaction and subsequent quantitative analysis of iNOS mRNA were performed on the cultures using beta-actin as an internal control. Immunohistochemical studies with an anti-iNOS monoclonal antibody were performed on the corresponding formalin-fixed paraffin-embedded prostatectomy tissue sections. We observed marked patient-to-patient variation in "normal" levels of iNOS mRNA. However, all six neoplastic cultures showed moderately to markedly higher mRNA levels than did their paired nonneoplastic cultures. In addition, iNOS protein levels were significantly higher in paraffin-embedded prostate cancer tissue sections than in adjacent nonneoplastic tissue. Overexpression of iNOS mRNA and protein levels is present in moderately differentiated prostate adenocarcinoma and may contribute to prostate cancer angiogenesis, tumor growth, and tumor-related immunosuppression.
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PMID:Expression of inducible nitric oxide synthase in paired neoplastic and non-neoplastic primary prostate cell cultures and prostatectomy specimen. 1285 39


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