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)

Mixed epithelial stromal tumor of the kidney (MEST)/adult cystic nephroma (CN) is a lesion characterized by epithelial lined tubular or cystic structures interspersed within a variably prominent, distinctive spindle-cell stroma. Although typically benign, cases with malignant features have been reported. Herein, we report a MEST/CN with malignant stromal features and rhabdoid differentiation arising in the left kidney of an 84-year-old woman. Histologically, the tumor displayed multiple tubules and variably sized cystic structures lined by benign epithelium with an intervening malignant-appearing spindle-cell stroma. The malignant stroma displayed condensation in the regions surrounding the epithelial component consistent with the ovarian-like stroma typically observed in MEST/CN. In addition, the stromal cells displayed extensive rhabdoid differentiation. Immunohistochemical analysis revealed strong expression of cytokeratin 7, CAM 5.2, AE1/AE3, wide-spectrum keratin, and epithelial membrane antigen by the epithelial component. The stromal component displayed strong immunohistochemical expression of WT-1, CD-99, CD-56, INI1, and estrogen receptor; focal actin positivity; and was negative for desmin, myogenin, and progesterone receptor. Analysis by reverse transcriptase polymerase chain reaction failed to identify the SYT-SSX1 or SYT-SSX2 fusion transcripts characteristic of synovial sarcoma. To our knowledge, this represents the first report in the literature of malignant MEST with rhabdoid features and suggests that this entity should be considered in the diagnosis of renal stromal malignancies with prominent rhabdoid features.
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PMID:Malignant mixed epithelial and stromal tumor of the kidney with rhabdoid features: report of a case including immunohistochemical, molecular genetic studies and comparison to morphologically similar renal tumors. 1770 62

Osteoporotic women exhibit high frequency of alveolar bone loss and low bone density. Estrogen deficiency, which is vital in the pathogenesis of postmenopausal osteoporosis, has received increasing attention in the studies related to the periodontal diseases. Similar to most hormones, estrogen exerts its influence by binding to specific receptors, estrogen receptor (ER)-alpha and -beta. The periodontal ligament cells (PDLcs) are very important in maintaining the integrity of the periodontal tissue, which is the connective tissue located between the alveolar bone and the root surface of tooth. In this study, we evaluated the effects of estrogen deficiency on the alveolar bone in ovariectomized rats by histometric measurement of attachment level in vivo. Using the reverse transcriptase polymerase chain reaction (RT-PCR) and Western-blot procedure, we also detected mRNA and protein products of ERs and investigated the effects of estrogen on bone-forming capability by monitoring alkaline phosphatase (ALP) activity and osteocalcin production in cultured human PDLcs. Our results demonstrated that both ER-alpha and -beta were expressed in PDLcs. Moreover, when exposed to 17-beta estradiol, PDLcs exhibited positive modulation on ALP activity and osteocalcin production. The study suggests that estrogen and ERs may play an important role in periodontal diseases.
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PMID:The expression of estrogen receptors and the effects of estrogen on human periodontal ligament cells. 1780 34

Currently, there is no effective therapy for estrogen independent breast cancer. MDA-MB-231 is an estrogen receptor negative highly invasive human breast cancer cell line and has been used as a relevant model system to evaluate drugs with chemopreventive potential against highly invasive breast cancer phenotypes. Epidemiological studies though inconclusive have shown that consumption of Green Tea Polyphenols (GTP) reduces the incidence and progression of breast cancer. Green tea is an important source of antioxidants that may be useful for chemoprevention of cancer. Recently published preclinical study from our lab suggested that GTP and EGCG treatment inhibit proliferation and induce apoptosis of MDA-MB-231. In this study, we have evaluated apoptotic and anti-invasive activity of green tea polyphenols (GTP) and its principal constituent Epigallocatechin gallate (EGCG) in MDA-MB-231 human breast cancer cell line. In in vitro human breast cancer model, EGCG and GTP induced apoptosis and significantly decreased invasion of breast cancer cells. Western blotting of MDA-MB-231 cell lysates from EGCG and GTP treated and untreated control revealed an increase in bax, reduction in bcl2 and PARP cleavage. Quantitative fluorescence labeling resulted in a 24-28% reduction in invasion through matrigel by EGCG and 15-23% reduction by GTP in a dose dependent manner. Focussed microarray analysis and reverse transcriptase polymerase chain reaction and zymogram analysis revealed inhibition of MMP-9 expression by polyphenol treatment. Furthermore, AKT was found to be inhibited both at the RNA and protein level by polyphenol treatment. Moreover EGCG and GTP decreased AKT phosphorylation as found out by Western blotting for Phospho-AKT (Ser-473). beta-catenin level was found to be decreased both in cytoplasm and nucleus. For the first time we report the connection of beta-catenin and AKT modulation by GTP and EGCG as a possible mechanism for the induction of apoptosis in human breast cancer cells and also inhibition in their invasive capacity.
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PMID:Green tea polyphenol and epigallocatechin gallate induce apoptosis and inhibit invasion in human breast cancer cells. 1805 61

Tamoxifen treatment of estrogen-dependent breast cancer ultimately loses its effectiveness due to the development of resistance. From a functional screen for identifying genes responsible for tamoxifen resistance in human ZR-75-1 breast cancer cells, fibroblast growth factor (FGF) 17 was recovered. The aim of this exploratory study was to assess the predictive value of FGF17 and the receptors FGFR1-4 for the type of response to tamoxifen treatment (clinical benefit) and the duration of progression-free survival (PFS) in patients with recurrent breast cancer. mRNA levels of FGF17 and FGFR1-4 were quantified by real-time reverse transcriptase PCR in 285 estrogen receptor-positive breast carcinomas with clinical follow-up. All patients had recurrent disease and were treated with tamoxifen as first-line systemic therapy for local or distant relapse. FGF17 and FGFR1-3 mRNA levels had no significant predictive value for this group of patients. However, high FGFR4 mRNA levels analyzed as a continuous log-transformed variable predicted poor clinical benefit (odds ratio=1.22; P=0.009) and shorter PFS (hazard ratio=1.18; P<0.001). In addition, in multivariable analysis, the predictive value of FGFR4 was independent from the traditional predictive factors. Our analyses show that FGFR4 may play a role in the biological response of the tumor to tamoxifen treatment. In addition, as altered expression of FGF17 causes tamoxifen resistance in vitro, the FGF signaling pathway could be a valuable target in the treatment of breast cancer patients resistant to endocrine treatment.
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PMID:Fibroblast growth factor receptor 4 predicts failure on tamoxifen therapy in patients with recurrent breast cancer. 1831 Feb 79

Mutations in the BRCA1-interacting DEAH helicase Brip1 confer an increased risk of breast cancer. In the present study we aimed to unravel the transcriptional control of Brip1 and to determine its expression levels in a set of 101 primary invasive breast carcinomas. Transcription of Brip1 was found to be cell growth-related and controlled by the E2F/retinoblastoma (Rb) pathway through a conserved E2F-responsive site. Repression of Brip1 expression by the cell growth-inhibiting compound 1alpha,25-dihydroxyvitamin D3 depended on this same E2F-responsive site. In spite of its role as a tumor suppressor, both quantitative reverse transcriptase-PCR analyses and immunohistochemical stainings showed significantly elevated Brip1 expression levels in grade 3 tumors as compared to grade 1 or 2 carcinomas. Furthermore, increased Brip1 transcript levels were found in tumors with an estrogen receptor-negative, progesterone receptor-negative or HER-2-positive status. In conclusion, these data show that Brip1 is a genuine target gene for the E2F/Rb pathway and that elevated expression levels of Brip1 are detected in primary invasive breast carcinomas with unfavorable characteristics.
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PMID:Expression of the BRCA1-interacting protein Brip1/BACH1/FANCJ is driven by E2F and correlates with human breast cancer malignancy. 1834 34

Oncotype DX is a commercially available reverse transcriptase-polymerase chain reaction based assay that provides a Recurrence Score (RS) and has been shown to provide prognostic and predictive information in estrogen receptor-positive lymph node-negative breast cancers. Independent studies of its utility in routine practice are lacking. Slides and surgical pathology reports from 42 cases of breast carcinomas evaluated by Oncotype DX were retrospectively reviewed to determine patient age, tumor size, histologic grade, estrogen and progesterone receptor (ER and PR) and ERBB2 (HER-2/neu) data, with ER and PR reported as a semi-quantitative score reflecting both intensity of staining and proportion of positive cells. We show here that Recurrence Score is significantly correlated with tubule formation, nuclear grade, mitotic count, ER immunohistochemical score, PR immunohistochemical score, and HER-2/neu status, and that the equation RS=13.424+5.420 (nuclear grade) +5.538 (mitotic count) -0.045 (ER immunohistochemical score) -0.030 (PR immunohistochemical score) +9.486 (HER-2/neu) predicts the Recurrence Score with an R2 of 0.66, indicating that the full model accounts for 66% of the data variability. Although the Oncotype DX Recurrence Score holds potential, further validation of its independent value beyond that of histopathologic analysis is necessary before it can be implemented in clinical decision making.
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PMID:Histopathologic variables predict Oncotype DX recurrence score. 1836 Mar 52

Corticotropin-releasing hormone (CRH) plays a central role in controlling stress response. In this study, we aimed to identify the regulatory effect of estrogen receptor (ER) on CRH and the underlying mechanism. We investigated the regulation of CRH mRNA in the BE(2)-C cell line, a human neuroblastoma cell line which express endogenous CRH. Quantitative reverse transcriptase-polymerase chain reactions showed that in the presence of estradiol overexpressing ER alpha or ER beta in BE(2)-C cells increased the transcription of CRH. Chromatin immunoprecipitation assays in this cell line also showed that both ER alpha and ER beta can be recruited to the CRH promoter with the treatment of estradiol. However, electrophoretic mobility shift assays did not show direct binding between estrogen receptors and two estrogen response elements (ERE) half sites in the CRH promoter. To clarify the regulatory mechanism, site-directed mutagenesis and reporter gene assay in the CHO cell line were used. When the ERE half sites and the cAMP regulatory element (CRE) in the CRH promoter were disrupted, ER-mediated up-regulation of CRH promoter activity reduced. Between the two ERE half sites studied, the -316 ERE half site contributed more to the constitutive CRH expression induced by ER. In summary, our results confirm the stimulation of ER alpha and ER beta on CRH expression and demonstrate the important roles of the ERE half sites and CRE for the action of ER alpha and ER beta.
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PMID:Estrogen receptor-alpha and -beta regulate the human corticotropin-releasing hormone gene through similar pathways. 1859 42

Endometriosis is a debilitating disease in which apoptotic, genetic, immunological, angiogenic and environmental factors have been implicated. Endocrine-disrupting agents (e.g. dioxins) might be involved. Dioxins, via the arylhydrocarbon receptor (AhR), induce estrogen-metabolizing enzymes CYP1A1 and CYP1B1. Elevated expression of gamma-SYNUCLEIN (gamma-SYN) has been associated with hormone-related conditions. Tissue sets consisting of eutopic and ectopic (ovarian) endometrium from patients with stage 3 or 4 endometriosis were obtained. Following RNA extraction and reverse transcription, quantitative real-time reverse transcriptase-polymerase chain reaction was performed for anti-apoptotic B-cell leukaemia/lymphoma 2 (BCL-2), CYP1A1, CYP1B1, estrogen receptor (ER)alpha, ER beta and gamma-SYN. Immunohistochemical analyses for gamma-syn, ER alpha, ER beta and CYP1A1 were also conducted. A 3-9-fold increase in intra-individual expression of CYP1A1 in ectopic (ovarian) endometrium compared with eutopic tissue was observed; immunohistochemical analyses pointed to CYP1A1 being localized to the glandular epithelium. This intra-individual expression profile was not observed for CYP1B1 or BCL-2. However, a 5-53-fold intra-individual increase in gamma-SYN expression was also demonstrated in six of nine tissue sets (a further two showed an increase that was not considered significant) when comparing ectopic to eutopic endometrium; gamma-syn positivity was associated with endothelial cells. An elevation in ER beta was also noted when comparing ectopic to eutopic endometrium; with regard to ER alpha, this was inconsistent. These results suggest an up-regulation of dioxin-inducible CYP1A1 and gamma-SYN occurs in endometriosis. Whether gamma-syn may be a novel diagnostic marker for endometriosis remains to be ascertained.
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PMID:Elevated expression of CYP1A1 and gamma-SYNUCLEIN in human ectopic (ovarian) endometriosis compared with eutopic endometrium. 1884 43

Exposure of maternal mice to inorganic arsenic through the drinking water induces liver tumors and aberrant gene expression in offspring when they reach adulthood. To help define if these are direct fetal effects of arsenic, fetal liver cells were isolated from untreated mice at gestation day 13.5 by mechanical dissection and centrifugation. Two hours after seeding the cells on collagen1-coated plates in William E media containing 10% fetal bovine serum, 1x ITS (insulin, transferrin, and selenium) and antibiotics, inorganic arsenite (0, 0.1, 0.3, and 1.0 microM) was added to the fresh media for 72 h. Cell morphology and viability were not significantly altered by these arsenic concentrations. At the end of arsenic exposure, cells were harvested into Trizol, and total RNA was extracted, purified, and subjected to real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Arsenite exposure produced a concentration-dependent induction of heme oxygenase-1 (up to eight-fold) and metallothionein-1 (up to five-fold), indicative of stress response to adapt to arsenic insult. Expression of genes related to steroid metabolism, such as 17beta-hydroxysteroid dehydrogenase-7 (HSD17beta7) and Cyp2a4, were increased approximately two-fold, together with increases in estrogen receptor-alpha (ER-alpha) and ER-alpha-linked genes, such as anterior gradient-2, keratin 1-19, and trefoil factor-3. Arsenic in vitro induced a three-fold increase in the expression of alpha-fetoprotein (AFP), a biomarker associated with transplacental arsenic-induced mouse liver tumors. Thus, exposure of mouse fetal liver cells to arsenic induces adaptive responses and aberrant gene expression, which could alter genetic programming at a very early life stage, potentially contributing to tumor formation much later in life.
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PMID:Arsenic-induced aberrant gene expression in fetal mouse primary liver-cell cultures. 1899 36

During mouse embryonic development, oocytes develop in germline cysts, formed by several rounds of cell division followed by incomplete cytokinesis. Shortly after birth, cysts break down and individual oocytes are enclosed by granulosa cells to form primordial follicles. At the same time, two-thirds of the oocytes die by apoptosis with only one-third surviving. We have previously shown that the steroid hormones, estradiol (E(2)), and progesterone as well as the phytoestrogen genistein can inhibit cyst breakdown and primordial follicle assembly. However, the mechanisms by which steroid hormones regulate oocyte cyst breakdown and selective oocyte survival are unknown. Here, we confirmed the expression of estrogen receptor (ER) mRNA and protein in neonatal mouse ovaries using reverse transcriptase-PCR, western blotting, and immunocytochemistry. We then used ER-specific agonists and antagonists to understand the mechanism of estrogen signaling. 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol, an ER alpha-selective agonist, and 2,3-bis(4-hydroxyphenyl)-propionitrile, an ER beta-selective agonist, both inhibited cyst breakdown in organ culture, suggesting that E(2) can signal through both the receptors to regulate cyst breakdown. ICI 182,780, an ER antagonist, completely blocked E(2)'s action. 1,3-bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole dihydrochloride, an ER alpha-specific antagonist, fully blocked E(2)'s effect on oocyte cyst breakdown and primordial follicle assembly and (R,R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol, an ER beta-specific antagonist, partially blocked E(2), further supporting the idea that both receptors are involved in estrogen signaling in neonatal oocyte development. E(2) conjugated to BSA, which can only exert effects at the membrane, was able to inhibit cyst breakdown, implying that E(2) could also function through a membrane-bound ER to regulate cyst breakdown.
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PMID:Estrogen can signal through multiple pathways to regulate oocyte cyst breakdown and primordial follicle assembly in the neonatal mouse ovary. 1950 48


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