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)

Rheumatoid arthritis (RA) is a disease characterized primarily by chronic inflammatory synovitis and is well-known to be associated with significant sex differences in its prevalence and clinical features. Sex steroids have been proposed to be involved in the pathogenesis of RA, but details pertaining to the expression of sex steroid receptors in RA synovial tissue have yet to be fully characterized. In the present study, we examined oestrogen receptor (ER) alpha, ERbeta, progesterone receptor (PR) and androgen receptor (AR) mRNA expression using real-time reverse transcriptase-PCR (RT-PCR) in eight female RA synovial tissues and six female synovial tissues without inflammation, and determined immunolocalization of ERalpha, ERbeta, PR-A, PR-B and AR using immunohistochemistry in synovial tissues obtained from 22 RA patients. Real-time RT-PCR analysis demonstrated the expression of ER, PR and AR mRNAs in both RA and non-inflamed synovial tissues. Relative abundance of ER mRNAs was significantly higher in RA synovial tissue than non-inflamed synovial tissue (P<0.05). In addition, the relative ERalpha/ERbeta mRNA expression ratio was significantly lower in RA than non-inflamed synovial tissue (RA, 2.34 +/- 1.60; and non-inflamed, 20.7 +/- 19.1; P<0.05). There were no significant differences in relative abundance of PR mRNA. Relative abundance of AR mRNA was significantly lower in RA (P<0.05). Immunoreactivity for ERalpha, ERbeta, PR-B and AR was detected in the lining cells, inflammatory cells and fibroblasts in all the patients examined. The labelling indices for ERbeta and PR-B were more abundant in both lining cells (ERbeta, 54.2 +/- 12.2%; PR-B, 73.6 +/- 18.9%) and inflammatory cells (ERbeta, 74.6 +/- 16.2%; PR-B, 75.9 +/- 16.1%) than in fibroblasts (ERbeta, 36.5 +/- 15.6%; PR-B, 49.4 +/- 18.0%). Labelling indices for ERalpha and AR were significantly higher in lining cells (ERalpha, 14.4 +/- 8.6%; AR, 31.2 +/- 11.3%) and fibroblasts (ERalpha, 12.1 +/- 7.5%; AR, 20.1 +/- 9.6%) than those in inflammatory cells (ERalpha, 5.7 +/- 3.3%; AR, 9.2 +/- 4.4%). There were significant differences (P<0.05) in the labelling indices for ERalpha, ERbeta and PR-B between men and women under 50 years of age in fibroblasts of RA synovial tissues. These results indicate that sex steroid receptors are present in RA and non-inflamed synovial tissues, including inflammatory cells in RA, and suggest that sex steroids may play important roles in the regulation of inflammation of RA synovial tissue.
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PMID:Sex steroid receptors in rheumatoid arthritis. 1457 May 89

Throughout the last decade many laboratories have shown that mRNA levels in formalin-fixed and paraffin-embedded (FPE) tissue specimens can be quantified by reverse transcriptase-polymerase chain reaction (RT-PCR) techniques despite the extensive RNA fragmentation that occurs in tissues so preserved. We have developed RT-PCR methods that are sensitive, precise, and that have multianalyte capability for potential wide use in clinical research and diagnostic assays. Here it is shown that the extent of fragmentation of extracted FPE tissue RNA significantly increases with archive storage time. Probe and primer sets for RT-PCR assays based on amplicons that are both short and homogeneous in length enable effective reference gene-based data normalization for cross comparison of specimens that differ substantially in age. A 48-gene assay used to compare gene expression profiles from the same breast cancer tissue that had been either frozen or FPE showed very similar profiles after reference gene-based normalization. A 92-gene assay, using RNA extracted from three 10- micro m FPE sections of archival breast cancer specimens (dating from 1985 to 2001) yielded analyzable data for these genes in all 62 tested specimens. The results were substantially concordant when estrogen receptor, progesterone receptor, and HER2 receptor status determined by RT-PCR was compared with immunohistochemistry assays for these receptors. Furthermore, the results highlight the advantages of RT-PCR over immunohistochemistry with respect to quantitation and dynamic range. These findings support the development of RT-PCR analysis of FPE tissue RNA as a platform for multianalyte clinical diagnostic tests.
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PMID:Measurement of gene expression in archival paraffin-embedded tissues: development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay. 1469 16

The effect of the dietary background of phytoestrogens on the outcome of rodent bioassays used to identify and assess the reproductive hazard of endocrine-disrupting chemicals is controversial. Phytoestrogens, including genistein, daidzein, and coumestrol, are fairly abundant in soybeans and alfalfa, common ingredients of laboratory animal diets. These compounds are weak agonists for the estrogen receptor (ER) and, when administered at sufficient doses, elicit an estrogenic response in vivo. In this study, we assessed the potential estrogenic effects of dietary phytoestrogens at the gene expression level, together with traditional biologic end points, using estrogen-responsive tissues of the immature female rat. We compared the gene expression profile of the uterus and ovaries, as a pool, obtained using a uterotrophic assay protocol, from intact prepubertal rats fed a casein-based diet (free from soy and alfalfa) or a regular rodent diet (Purina 5001) containing soy and alfalfa. Estrogenic potency of the phytoestrogen-containing diet was determined by analyzing uterine wet weight gain, luminal epithelial cell height, and gene expression profile in the uterus and ovaries. These were compared with the same parameters evaluated in animals exposed to a low dose of a potent ER agonist [0.1 microg/kg/day 17alpha-ethynyl estradiol (EE) for 4 days]. Exposure to dietary phytoestrogens or to a low dose of EE did not advance vaginal opening, increase uterine wet weight, or increase luminal epithelial cell height in animals fed either diet. Although there are genes whose expression differs in animals fed the soy/alfalfa-based diet versus the casein diet, those genes are not associated with estrogenic stimulation. The expression of genes well known to be estrogen regulated, such as progesterone receptor, intestinal calcium-binding protein, and complement component 3, is not affected by consumption of the soy/alfalfa-based diet when assessed by microarray or quantitative reverse transcriptase-polymerase chain reaction analysis. Our results indicate that although diet composition has an impact on gene expression in uterus and ovaries, it does not contribute to the effects of an ER agonist.
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PMID:Impact of the phytoestrogen content of laboratory animal feed on the gene expression profile of the reproductive system in the immature female rat. 1553 37

Telomerase, a ribonucleoprotein enzyme that functions as a reverse transcriptase, is detected exclusively in immortal cells such as germ cells, stem cells and cancer cells. Telomerase activity is present in almost all human cancers. Telomerase activation is considered to be essential to maintain the integrity of the replicating tumor cell and to establish immortality. Based on this concept antiestrogen should initially regulate estrogen-stimulated telomerase but the enzyme would be expected to be constitutive in tamoxifen-resistant tumor cells. We have studied the estrogen regulation of telomerase in T47D:A18 breast cancer cells with a TRAPEZE Telomerase detection kit. Estradiol significantly increased telomerase activity after a 2-day treatment. Telomerase activity induced by estradiol was up to 10-fold higher within 4 days. Antiestrogens 4-hydroxytamoxifen (4-OHT) and ICI 182,780 were inactive alone and significantly blocked estradiol-stimulated increase in telomerase. These effects were correlated with changes in cell replications and changes in the cell cycle. In contrast, 4-OHT resistant T47D:A18 cells (T47D:A18/4-OHT, cultured in 1 microM 4-OHT for 6 months) grew spontaneously and had no changes in the cell cycle with estrogen treatment. The estrogen receptor (ERalpha) was present and still regulated at an estrogen responsive luciferase reporter gene with estrogen despite the fact that progesterone receptor was not increased in response to estradiol in T47D:A18/4-OHT cells. However, telomerase activity was increased about 40-fold in T47D:A18/4-OHT cells and this was not regulated by ICI 182,780. We conclude that the differential regulation of telomerase gene might be an important transition for tamoxifen resistance in T47D:A18 breast cancer cells.
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PMID:Deregulation of estrogen induced telomerase activity in tamoxifen-resistant breast cancer cells. 1621 Dec 43

A common feature of human breast oncogenesis is cell cycle deregulation. The expression of cyclins D1 and D3 was examined during estradiol-17beta (E(2))-induced mammary tumorigenesis in female August Copenhagen Irish (ACI) rats. Low serum E(2) levels ( approximately 60-120 pg/ml) were sufficient to induce mammary gland tumors (MGTs) that remarkably resemble human ductal breast cancer (BC) at the histopathologic and molecular levels. Western blot analysis of the E(2)-induced MGTs revealed a marked rise in cyclins D1 (24-fold), D3 (9-fold) and cdk4 (3-fold) expression compared with age-matched untreated controls. Small focal dysplasias with large, pale staining nuclei were commonly seen at 3-3.6 months, large focal dysplasias, including atypical ductal hyperplasia at 3.6-4.3 months, ductal carcinoma in-situ (DCISs) at 4.3-5.0 months, and 100% incidence of invasive ductal BC/frank tumors at 5-6 months were detected after E(2) treatment. Immunohistochemical analysis of serial sections of focal dysplasias, DCISs and invasive ductal carcinomas showed overexpression of cyclins D1, D3, estrogen receptor-alpha (ERalpha) and progesterone receptor (PR). However, cyclin D3 expression, unlike D1, was confined essentially to early pre-malignant lesions (focal dysplasias and DCISs) and primary MGTs with <1-5% of resting and normal hyperplastic breast cells staining positive. The kinase activity for cyclins D1 and D3, using retinoblastoma (Rb) as a substrate, in E(2)-induced MGTs and their binding to cdk4 was significantly elevated. Semi-quantitative reverse transcriptase PCR analysis of the E(2)-induced MGTs exhibited increased expression of cyclins D1 (2.9-fold) and D3 (1.4-fold) mRNA, indicating that their elevated protein expression was due in part to an increase in mRNA transcription. However, when analyzed by quantitative real-time Q-PCR, these genes were not amplified. These data indicate that in female ACI rat mammary glands, E(2)-induced pre-malignant lesions differentially and selectively express cyclins D1 and D3, thus contributing to a distinct growth advantage of these pre-neoplasias relative to E(2)-elicited normal hyperplasia.
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PMID:Overexpression of cyclins D1 and D3 during estrogen-induced breast oncogenesis in female ACI rats. 1631 Dec 45

The purpose of this study was to establish the eventual presence of progesterone receptor (PGR) and oestrogen receptor (EGR) in human middle-ear cholesteatoma (MECh) tissues and to compare their expression between male and female patients. An immunohistochemical technique was employed for detection of PGR- and EGR-specific immunoreactivity in MECh samples using formalin-fixed paraffin-embedded tissue sections. The positive results were verified with reverse transcriptase polymerase chain reaction (RT-PCR). The morphological study revealed stable expression of PGR in suprabasal layers of all cholesteatoma samples. Weaker immunoreactivity for PGR was demonstrated in external auditory canal skin (EACS) samples in comparison with MECh, while PGR-specific staining was not observed in retroauricular skin (RAS) samples. EGR was detected only at mRNA levels. Stronger expression of EGR PCR products was disclosed in female cholesteatoma samples, while PGR mRNA was predominantly detected in male cholesteatoma specimens. Our preliminary experimental results give us ground to assume that female sex hormones may stimulate proliferation and affect differentiation of MECh keratinocytes.
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PMID:Expression of female sex hormone receptors in human middle-ear cholesteatomas. 1635 54

Human mammaglobin (hMAM) has recently been recognized as a breast associated glycoprotein. Although the biological role of hMAM is unknown, it has been previously reported that hMAM gene expression is a marker of low biological and clinical aggressiveness of breast cancer (BC). In this study, 148 cases of BC tissues were investigated for hMAM mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). In order to evaluate its prognostic value, hMAM was correlated with age of patients, type and size of tumor, nodal stage, histologic grade, c-erbB-2 over expression, Ki67 labelling index, estrogen receptor (ER) status and progesterone receptor (PGR) status. Fisher's exact test was used to examine the association between different parameters and hMAM. hMAM was expressed in 138/148 (93%) of BC tissues examined. Among the 10 hMAM negative cases, 8 were invasive ductal carcinomas (microscopically higher G3 grade) and 2 infiltrating lobular carcinomas. We found a significant association (p = 0.020) between absence of hMAM mRNA and G3 histologic grade but not with any other prognostic parameters studied. The present study indicates that lack of hMAM expression is restricted to the BC with G3 grading. Further studies are needed to clarify the biological basis and the clinical significance of our results.
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PMID:Relationship between human mammaglobin mRNA expression in breast cancer tissue and clinico-pathologic features of the tumors. 1676 20

Ovarian progesterone (Prog) is an essential steroid hormone for the secretion of GnRH and reproductive behavior. It exerts primary effects through the progesterone receptor (PR). When analyzed separately in vitro, PR isoforms (PR-A, PR-B) display striking differences in transcriptional activity. The present study was undertaken to determine the in vivo impact of each isoform on hypothalamic function in female mice with ablation of a single isoform, either PR-A or PR-B. To this end, we used single-cell RNA analyses, reverse transcriptase real-time (q)PCR mRNA analyses of punched-out tissue, immunohistochemistry, and reproductive behavior. We provide evidence for the requirement of PR-A in individual ventrolateral ventromedial nucleus (vlVMN) neurons for Prog-facilitated proceptive and receptive behaviors in estrogen benzoate (EB)-primed females and the reciprocal male interactions. We clarify histological and molecular mechanisms of PR isoform activity by showing that (1) PR-A is predominant in individual vlVMN neurons controlling female lordosis circuitry, whilst (2) PR-B is predominant in those VMN subdivisions that provide for amplification of PR-A activity. We go on to demonstrate that PR-A is dominant in the anteroventral periventricular nucleus but not the arcuate nucleus that feed fibers into and around the VMN. In the medial preoptic area, high levels of GnRH RNA in EB-primed PR-A-expressing mice were seen coincident with increased plasma LH levels. Two consecutive GnRH pulses enhanced LH only in primed PR-A-expressing females. In all, the findings are consistent with the hypothesis that hypothalamic PR-A-mediated genomic activities result in reproductive behavior coordinated with ovulation.
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PMID:Hypothalamic progesterone receptor-A mediates gonadotropin surges, self priming and receptivity in estrogen-primed female mice. 1724 68

In addition to new tumour antigens, new prognostic and diagnostic markers are needed for common cancers. In this study, we report the expression of Dickkopf-1 (DKK1) in multiple common cancers. This constitutes a comprehensive analysis of the DKK1 expression profile. Dickkopf-1 expression was evaluated by classical and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbant assay for protein determination, in cancer lines and clinical specimens of several cancer origins. For breast cancer, expression was correlated with clinicopathological parameters. Dickkopf-1 expression was confirmed in several cancer cell lines derived from breast and other common cancers. Dickkopf-1 protein secretion was documented in breast, prostate and lung cancer lines, but was negligible in melanoma. Analysis of DKK1 expression in human cancer specimens revealed DKK1 expression in breast (21 out of 73), lung (11 out of 23) and kidney cancers (six out of 20). Interestingly, DKK1 was preferentially expressed in oestrogen and progesterone receptor-negative tumours (ER(-)/PR(-); P=0.005) and in tumours from women with a family history of breast cancer (P=0.024). Importantly, DKK1 protein production was confirmed in multiple breast cancer specimens that were positive by RT-PCR. This work establishes DKK1 as a potential prognostic and diagnostic marker for cohorts of breast cancer patients with poor prognosis. Dickkopf-1 may also become a relevant candidate target for immunotherapy of different cancers.
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PMID:The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types. 1724 40

A variety of extraimmune system factors, including hormones, play a critical role in regulating immunity. Progesterone has been shown to affect immunity in rodents and humans, mainly at concentrations commensurate with pregnancy. These effects are primarily mediated via the progesterone receptor (PR), which acts as a transcription factor, although non-genomic effects of PR activation have been reported. In this study, we evaluated the effects of progesterone on rat dendritic cells (DCs) at ranges encompassing physiologic and pharmacologic concentrations to determine whether progesterone plays a role in modulating DC-mediated immune responses. DCs were derived by culturing rat bone marrow cells in granulocyte macrophage colony-stimulating factor and IL-4. Cells were analyzed for expression of PR using FACS analysis, real-time reverse transcriptase-PCR and fluorescent microscopy. Progesterone treatment of LPS-activated, mature bone marrow-derived dendritic cells (BMDCs) suppressed production of the pro-inflammatory response-promoting cytokines tumor necrosis factor-alpha and IL-1beta in a dose-dependent manner but did not affect production of the pro-inflammatory response-inhibiting cytokine IL-10. Treatment of cells with progesterone also resulted in down-regulation of co-stimulatory molecule CD80 and MHC class II molecule RT1B expression. In addition, progesterone inhibited DC-stimulated proliferation of T cells. Suppression of pro-inflammatory response-promoting cytokine production by progesterone was prevented using the PR antagonist RU486. There was no dose-dependent effect of progesterone treatment on immature DC capacity to take up antigenic peptide. These data indicate that progesterone directly inhibits mature rat BMDC capacity to drive pro-inflammatory responses. This mechanism could contribute to or account for some of the differential expression of autoimmune/inflammatory disease in females.
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PMID:Progesterone inhibits mature rat dendritic cells in a receptor-mediated fashion. 1728 56


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