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)

The insulin-like growth factor (IGF) system is thought to function as a mediator of steroid hormone actions in the endometrium. IGFs (IGF-I and IGF-II) are also potent mitogens in endometrial cancer. The biological actions of IGFs are modulated by specific binding proteins (IGFBP)--6 cloned and sequenced so far--which may either inhibit or enhance the effects of IGF at the cellular level. In the endometrium, IGFBP-1 gene expression is stimulated by progesterone and inhibited by insulin, while IGFBP-1 inhibits the mitogenic action of IGF-I. In this study, we used a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) to investigate IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5 and IGFBP-6 gene expression in endometrial cancer tissues. Endometrial cancer tissue samples were collected from 20 women (aged 54-79 yrs) with stage I to II well-differentiated endometrial adenocarcinoma. Samples of normal endometrium (n = 14) obtained from women undergoing tubal ligation in various phases of the menstrual cycle, and normal early-pregnancy endometrium (decidua) were studied for comparison. In endometrial cancer tissues, the IGFBP-1 mRNA was undetectable or minimally expressed when studied by RT-PCR. The mean (+ SD) levels of IGFBP-2 and IGFBP-4 and IGFBP-5 mRNAs in endometrial cancer tissues did not differ from those in normal endometrium, in which no cyclic variation was observed, suggesting that the genes encoding IGFBP-2, IGFBP-4 and IGFBP-5 are not hormonally regulated in the endometrium. The IGFBP-6 mRNA expression showed a significant cyclic variation in normal endometrium, with low levels in late-proliferative and early- to mid-secretory phases and high expression in late-secretory and early-proliferative phases. In endometrial cancer tissues, the mean IGFBP-6 mRNA level was similar to that in cycling endometrium during the peri-ovulatory period. In summary, a continuous stimulation of the endometrial epithelial cells by IGFs with suppressed IGFBP-1 expression may lead to an imbalance in the IGF system of the endometrium and trigger an uncontrolled cell proliferation, ultimately resulting in malignant transformation.
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PMID:Suppressed expression of insulin-like growth factor binding protein-1 mRNA in the endometrium: a molecular mechanism associating endometrial cancer with its risk factors. 752 16

The expression of mRNAs for keratinocyte growth factor (KGF) (also called FGF-7) and its receptor was evaluated in normal human endometrium and myometrium as well as in myoma and in endometrial adenocarcinoma cell lines using reverse transcriptase polymerase chain reaction. Both KGF and its receptor mRNA are expressed in the human endometrium throughout the menstrual cycle, whereas fibroblast growth factor receptor 2 (FGFR-2) mRNA expression is low in this tissue. In endometrial stromal cell enriched preparations KGF mRNA dominates with little expression of KGF receptor (KGFR) and FGFR-2, whereas in the epithelial cell-enriched fraction the KGFR mRNA dominates. Human myometrium and myoma express mRNA for KGF, but not for KGFR. FGFR-2 is expressed in both myometrial and myoma tissues. None of the five endometrial adenocarcinoma cell lines studied expressed KGF mRNA, whereas all cell lines expressed mRNA for either KGFR or FGFR-2 or for both receptors. The results show a selective expression of KGFR and the closely related FGFR-2 in the human uterus with the former being expressed in the endometrium and the latter predominantly in the adjacent myometrium. In the endometrial tissue, selective expression of KGF in stromal cells and KGFR in epithelial cells supports the paracrine function of KGF in epithelial tissue.
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PMID:Differential expression of keratinocyte growth factor and its receptor in the human uterus. 824 6

Localization of tenascin-C in vivo and cell culture experiments in vitro have provided evidence for stromal production of tenascin-C in malignant tumors of a variety of organs. Here we raised the question of whether the mesenchymal stroma in the case of endometrial adenocarcinoma is the unique source of tenascin-C. Therefore, the expression of tenascin-C mRNA by human endometrial adenocarcinoma cells and endometrial stroma cells was investigated. Several preparations of endometrial stroma cells produced tenascin-C mRNA. Using a serum-free defined cell culture medium, production of tenascin-C mRNA could be increased by adding either serum or 20 ng TGF-beta/mL to the cell culture medium. Reverse transcriptase polymerase chain reaction analysis revealed that five out of six endometrial adenocarcinoma cell lines produced tenascin-C mRNA. Northern blot experiments and ribonuclease protection assays provided evidence that the number of copies of tenascin-C mRNA was small. Analysis of expressed splice variants by reverse transcriptase polymerase chain reaction analysis revealed the abundance of one major splice variant that lacked all potential alternatively spliced fibronectin type-III-like repeats. Regarding larger splice variants, all fragment sizes that could theoretically originate from seven alternatively spliced fibronectin type-III-like repeats were observed. Evaluating relative signal intensities, the splice variants containing a single fibronectin type-III-like repeat and the variant possessing all but one alternatively spliced repeats were most frequent. In summary, evidence is provided that tenascin-C can originate from both tissue compartments of the human endometrium stroma and (tumor) epithelium. Splice variant analysis revealed a high number of splice variants and a relative high proportion of variants that have so far been regarded as minor constituents of expressed tenascin-C.
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PMID:Expression of tenascin-C by human endometrial adenocarcinoma and stroma cells: heterogeneity of splice variants and induction by TGF-beta. 959 65

Telomerase is a reverse transcriptase that adds repetitive telomere sequences to the end of chromosomes, which is thought to be essential for cellular immortality and oncogenesis. The enzyme consists of three subunits: human telomerase reverse transcriptase (hTERT), human telomerase RNA (hTR), and telomerase protein 1 (TP1). The hTERT subunit determines the activity of telomerase as an enzyme and is detected in most human tumors and regenerative cells. But many studies have revealed that hTR and TP1 are expressed constitutively. This results suggest that the hTR and TP1 subunits may be potentially good markers of endogenous RNA control. Endometrial dating was determined from the pathomorphology of the endometrium and classified into normal proliferative endometrium, endometrial hyperplasia (simple, complex, and atypical), and endometrial adenocarcinoma. The analysis of the expression of the hTERT, TP1, and hTR telomerase subunits was performed by a quantitative polymerase chain reaction method, based on fluorescent TaqMan methodology (ABI Prism 7,700 Sequence Detection System) capable of measuring fluorescence in real time. The aim of the study was an analysis of the expression profiles of genes encoding hTR and TP1 telomerase subunits in normal endometrium, endometrial hyperplasia, and adenocarcinoma for the estimation of the possibility of once application in endogenous RNA control of gene analysis in the endometrium. The nonparametric Mann-Whitney U test and analysis of variance Friedman test were used to evaluate the variation in telomerase subunit mRNA level between normal endometrium, and endometrial hyperplasia and adenocarcinoma. The results confirm the hTR subunit expression as a good marker of endogenous control in quantitative analysis of gene transcription in endometrial tissue. TP1 subunit transcriptions have not been detected constitutively in our study.
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PMID:Human telomerase RNA as endogenous control in endometrial tissue. 1582 23

Urocortin (UCN) is a 40-amino acid neuropeptide sharing 45% sequence homology with corticotropin-releasing factor (CRF). The human endometrium expresses both UCN and CRF, and CRF/UCN receptors type-1 (CRF-R1) and -2 (CRF-R2). CRF-R1 activation inhibits cell growth and proliferation of a tumor cell line derived from the human endometrium, and the UCN signaling pathway has been implicated in tumorigenesis of several tissues. Therefore, we investigated whether UCN mRNA and peptide are expressed by human endometrial adenocarcinoma, and whether their expression changes compared to controls. Samples of well (grade 1; n = 6 endometrioid adenocarcinoma, of whom n = 1 with squamous differentiation, and n = 1 clear-cell carcinoma) and poorly differentiated (grade 3; n = 3 endometrioid adenocarcinoma) endometrial adenocarcinoma were collected from nine women (age range 61-79 years) enrolled at the time of diagnosis. Healthy endometrium was collected from postmenopausal women (controls; n = 13; age range 64-78 years), who underwent hysterectomy for uterine prolapse. Immunohistochemistry was used to evaluate cellular UCN localization, with the intensity of immunostaining scored on a subjective scale. Quantitative real-time reverse transcriptase (RT)-PCR analysis was used to estimate mRNA expression changes and restriction analysis was used to confirm PCR products identity. UCN mRNA expression was significantly reduced (P < 0.0001) in endometrial adenocarcinoma than in healthy controls. Immunoreactive UCN was found in luminal and glandular epithelial cells in healthy, but not in neoplastic samples. UCN mRNA and peptide expressions are decreased in endometrial adenocarcinoma. These data and the evidence that endometrial cancer expresses UCN receptors and UCN is involved in tumorigenesis of several tissues together suggest a role for UCN in endometrial tumoral cell growth and proliferation.
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PMID:Urocortin expression is downregulated in human endometrial carcinoma. 1683 14

Maspin is a member of the serpin family, whose expression is altered in neoplasia and malignancies of many tissues. Underexpression of maspin has been reported in breast and prostatic cancers, but in some cancers such as ovarian, colorectal and pancreatic carcinoma, it was found to be up-regulated. This study aimed at demonstrating the expression of maspin in human endometrial tissue and searching for any altered expression in endometrioid adenocarcinoma of the endometrium compared to normal endometrium. The expression level of the maspin gene was studied using reverse transcriptase-polymerase chain reaction (RT-PCR) performed on RNA extracted from 34 endometrial cancer samples (including 24 with FIGO stage I disease and 10 with FIGO stage III disease) and 28 normal endometrium in proliferative or secretory phases. Immunohistochemical staining was also performed on 10 cases of endometrial cancer (6 FIGO stage I cases and 4 FIGO stage III cases) as well as 15 normal endometrium. Semi-quantitative RT-PCR revealed that the expression of maspin was significantly up-regulated in both stage I (p<0.01) and stage III (p<0.01) endometrial cancer compared with normal endometrium. However, no significant difference in maspin expression was demonstrated between stage I and stage III endometrial cancer. Immunostaining of all tissue sections revealed an immunopositive signal in the nuclei of the normal or cancerous endometrial glandular cells. In 60% of the cancer cases, cytoplasmic staining was also evident. Our results suggested that there is up-regulated expression of maspin in endometrioid endometrial adenocarcinoma. Cytoplasmic immuno-expression of maspin is common in endometrial cancer. It may play a role in the malignant transformation of human endometrial tissue.
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PMID:Expression of maspin in endometrioid adenocarcinoma of endometrium. 1720 79