Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
11,379 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

Pig uterine luminal flushings contain at least four heparin-binding growth factors (HBGF) that stimulate fibroblast [3H]thymidine incorporation. One of these factors, which appeared to be a relatively minor HBGF, was eluted from heparin affinity columns by 1.0 M NaCl and was found to compete with 125I-epidermal growth factor (EGF) for binding to an endometrial carcinoma cell line. This EGF receptor (EGF-R)-binding property was abolished by an antiserum to heparin-binding EGF-like growth factor (HB-EGF) that specifically blocks binding of HB-EGF to the EGF-R. Reverse-phase HPLC resulted in the purification of two EGF-R-binding activities correlated with 13,500 and 17,000 M(r) proteins that reacted with an antiserum raised against residues 9-26 of human HB-EGF. Uterine extracts also contained an EGF-R-binding factor that was eluted from heparin by 1.0 M NaCl and was antagonized by HB-EGF antiserum. Endometrial mRNA subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR through the use of HB-EGF-specific primers yielded fragments of the predicted size. Cloning of the nested PCR product revealed a 380-bp porcine HB-EGF cDNA sequence that was 78-85% homologous to primate or rodent HB-EGF. HB-EGF was immunohistochemically localized primarily to the luminal epithelium in both pregnant and nonpregnant animals.
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PMID:Purification of heparin-binding epidermal growth factor-like growth factor from pig uterine luminal flushings, and its production by endometrial tissues. 753 97

It has been proposed that the biosynthesis of estrogens by the human endometrium may be of physiological significance during the menstrual cycle. Local estrogen production was also suggested to be important in the development of endometrial cancer; however, the presence or absence of aromatase enzyme activity in normal human endometrium is controversial. To address this issue, we used a sensitive technique capable of detecting mRNA transcripts present in only very low copy number. The polymerase chain reaction linked to reverse transcription (RT-PCR) was used to evaluate the presence or absence of aromatase cytochrome P450 (P450arom) transcripts in endometrial tissues (n = 7) and endometrial stromal cells (n = 9) under various culture conditions. RNA was isolated from four proliferative and three secretory tissue samples and from cultured endometrial stromal cells isolated from seven proliferative and two secretory endometria. Five sets of cultures were treated with medroxyprogesterone acetate (MPA), estradiol (E2), and forskolin. Additionally, RNA was isolated from decidualized endometrium obtained from a patient with tubal pregnancy. A single stranded cDNA was synthesized from total RNA using Moloney murine leukemia virus reverse transcriptase and a P450arom-specific oligonucleotide. The single stranded cDNA was used as a template for PCR and was amplified for 20-35 cycles using P450arom-specific primers. RNA from adipose tissue and placenta was amplified to provide positive controls, whereas myometrial RNA was used as a negative control. In two experiments involving two endometrial tissues and three sets of cells in culture, a rat P450arom cRNA was coamplified in each sample as an internal control to demonstrate that the remote possibility of RT-PCR failures in individual test samples cannot account for our negative results. By Southern or slot blot hybridization of the amplified fragments using human and rat P450arom-specific probes, we found no evidence for the presence of P450arom transcripts in normal endometrium, decidualized endometrium, or endometrial stromal cells in culture. In our hands, assay of aromatase activity using [3H]water release from [3H]androstenedione by endometrial stromal cells in culture treated with MPA and E2, did not reveal any detectable aromatase activity. The same cells responded to MPA plus E2 treatment by a significant increase in PRL secretion into the culture medium. Presently, RT-PCR is the most sensitive method available for the detection of specific mRNA species in low copy numbers. These findings are indicative of the absence of P450arom transcripts in normal human endometrium.
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PMID:Polymerase chain reaction amplification fails to detect aromatase cytochrome P450 transcripts in normal human endometrium or decidua. 768 41

It has been reported that interleukin-8 (IL-8) is secreted from the placental and decidual tissues and that IL-8 levels in the amniotic fluids are significantly elevated by chorioamnionitis or labor pain. The present study was aimed at defining the localization of IL-8 mRNA as well as IL-8 protein at the feto-maternal interface using in situ hybridization and immunohistochemical staining. Both IL-8 mRNA and protein were localized in cytotrophoblast, syncytiotrophoblast and Hofbauer cells of the placenta, decidual stromal cells, decidual lymphocytes and endometrial gland cells. IL-8 secretion from glandular cells has not previously been reported. In addition, we confirmed IL-8 mRNA expression and secretion of IL-8 by an endometrial cancer cell line (Ishikawa) using the reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) methods, respectively.
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PMID:Detection and localization of interleukin-8 mRNA and protein in human placenta and decidual tissues. 773 6

In this study, we used reverse transcriptase-polymerase chain reaction (RT-PCR) to compare the expression of mRNAs encoding endothelin-1 (ET-1), endothelin receptors type A (ETA-R) and type B (ETB-R) and ET-1-degrading enzyme neutral endopeptidase 24.11 (NEP) in 15 endometrial cancer tissues and 13 normal endometrial tissues. The relative levels of ET-1 mRNA in endometrial cancer tissues did not differ from those in normal endometrium. Both ETA-R and ETB-R mRNA levels were significantly lower in endometrial cancer tissue than in normal endometrium (P < 0.001). The complete lack of NEP mRNA in endometrial cancer tissues was in marked contrast to results from normal endometrium (P < 0.001). In conclusion, differential expression of mRNAs encoding ET-R and NEP in normal endometrium and endometrial cancer suggests that ET action is altered in endometrial cancer compared with normal endometrium.
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PMID:Decreased expression of messenger RNAs encoding endothelin receptors and neutral endopeptidase 24.11 in endometrial cancer. 781 49

In order to identify the possible role of the DCC gene in neoplasms of the human female reproductive tract, messenger RNA expression of the DCC gene was examined by reverse transcriptase-polymerase chain reaction, and expression of the DCC gene product was detected immunohistochemically. While histologically normal endometrium, cervical epithelium and ovary expressed detectable mRNA of the DCC gene, three of eight (37%) endometrial carcinomas, one of two (50%) cervical carcinomas and 9 of 22 (41%) ovarian malignant tumours had significantly reduced or negligible DCC expression, and another endometrial carcinoma and two other ovarian tumors underexpressed DCC when compared with histologically normal endometrial or ovarian tissues. Impaired DCC mRNA expression was detected more frequently in grade 3 ovarian epithelial tumours than in grade 1 tumours (P = 0.002). Loss of expression of the DCC gene product detected by immunohistochemistry significantly correlated with the loss of mRNA expression in ovarian carcinomas (P = 0.01 by chi-square test) or in both endometrial and ovarian carcinomas combined (P = 0.001). Loss of heterozygosity of the DCC gene was also evaluated by restriction fragment polymorphism analysis of the polymerase chain reaction-amplified DNA fragment. Loss of heterozygosity of the DCC gene was detected in one of seven (14%) informative cases of endometrial carcinomas, 1 of 11 (9%) informative cases of cervical carcinomas and two of six (33%) informative cases of ovarian tumours. These results demonstrate that inactivation of the DCC gene, especially by the loss of expression, plays a significant role in the aetiology of neoplasms of the human reproductive tract.
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PMID:Loss of expression and loss of heterozygosity in the DCC gene in neoplasms of the human female reproductive tract. 788 Jul 25

Recent results have shown that specific binding sites for luteinizing hormone-releasing hormone (LHRH) are present in biopsy samples of human endometrial cancer and in the human endometrial cancer cell lines Ishikawa and HEC-1A. The proliferation of these cell lines was retarded by LHRH analogs. The present study was undertaken to determine whether these endometrial tumor cells also produce LHRH or an LHRH-like peptide which could serve as natural ligand for the LHRH binding sites. Using a specific antibody, LHRH-immunoreactivity was detected in extracts of Ishikawa (426 +/- 84 fmol/10(6) cells) and HEC-1A (368 +/- 41 fmol/10(6) cells) cells. LHRH-like bioactivity of these samples was assessed in a rat pituitary cell culture system. The release of luteinizing hormone induced by endometrial cancer cell extracts corresponded to that obtained with comparable amounts of authentic LHRH. The expression of the mRNA for LHRH could be demonstrated by reverse transcriptase - polymerase chain reaction using specific primers according to the published sequence and by subsequent Southern blot analysis. The presence of immuno- and bioactive LHRH-like factors and the demonstration of expression of the mRNA for LHRH in two human endometrial cancer cell lines supports the concept of an autocrine regulatory system based on LHRH in endometrial cancer.
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PMID:Expression of luteinizing hormone releasing hormone and its mRNA in human endometrial cancer cell lines. 807 83

We studied the involvement of annexin V in the antiproliferative effects of gonadotropin-releasing hormone (GnRH) agonists on human endometrial cancer cell line HHUA. HHUA cell line expressed mRNA for GnRH receptors as assessed by reverse transcriptase-PCR with oligonucleotide primers. In the presence of buserelin, the proliferation of this cell line was significantly (P < 0.01) reduced to 60% of control after 72 hr. Peak intracellular concentrations of annexin V, equivalent to about twice the control value, were obtained after 48 hr exposure to buserelin. Intracellular annexin V concentration was increased not only by buserelin, but also by protein kinase C (PKC) activator. However, there was no increase in intracellular annexin V concentration when cells were incubated with PKC inhibitor before the addition of buserelin. The results suggest that GnRH agonists inhibit cell proliferation by increasing intracellular concentrations of annexin V, an effect mediated by the activation of PKC.
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PMID:Involvement of annexin V in antiproliferative effects of gonadotropin-releasing hormone agonists on human endometrial cancer cell line. 926 65

Two novel transcripts of human estrogen receptor (ER) have been identified that differ in the 5' untranslated sequence. It has previously been determined that an alternate ER transcript is generated from transcription initiated upstream of the main ER cap site (P1), and utilizes a splice acceptor site at +163. Here we report the isolation of 21 ER clones from a MCF7 cDNA library. Eleven of these clones correspond to transcripts that initiate at the P1 cap site, whereas the remaining 10 clones are derived from two previously unidentified ER transcripts (designated E and H) that both utilize the +163 splice acceptor site. A panel of breast and endometrial carcinoma cell lines were screened by reverse transcriptase-polymerase chain reaction (RT-PCR) for expression of the E and H transcripts. It was found that all ER-positive cell lines expressed both of the novel transcripts. In addition, 10 primary human breast cancers were analyzed, of which six expressed the E transcript and five abundantly expressed the H transcript. These data indicate that expression of ER in human breast cancers can be dependent upon an alternate promoter at least 20 kb upstream of the primary cap site for ER.
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PMID:Identification of two estrogen receptor transcripts with novel 5' exons isolated from a MCF7 cDNA library. 939 49

Long-term tamoxifen therapy is associated with increased risk of uterine endometrial cancer and benign alterations. Tamoxifen is metabolized to reactive intermediates by endometrial tissue, and tamoxifen therapy-induced DNA adducts have been found in human endometrium. Since metabolic activation is often catalyzed by cytochrome P450 (CYP) enzymes, the expression profile of individual xenobiotic-metabolizing CYP genes was studied in human uterine endometrium by reverse transcriptase-polymerase chain reaction. The following CYP mRNAs were detected: CYP2B6, CYP2C, CYP2E1, CYP3A4, CYP3A5, CYP4B1, and CYP11A. Amplification of CYP1A1, CYP1A2, CYP2A6, CYP2D6, CYP2F1, CYP3A7, and CYP19 was not found. CYP3A5 and CYP4B1 transcripts were found only in samples from premenopausal women. These data suggest that the human endometrial epithelium has the potential of producing CYP enzymes known to generate genotoxic intermediates from tamoxifen and metabolites that affect oestrogen receptors.
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PMID:Expression of cytochrome P450 genes encoding enzymes active in the metabolism of tamoxifen in human uterine endometrium. 949 38


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