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 nuclear receptor coactivator amplified in breast cancer 1 (AIB1) and its more active isoform AIB1-Delta3 are overexpressed in breast cancer and preneoplastic breast tissue. However, the impact of these proteins on the transcriptional activity of natural estrogens or selective estrogen receptor modulators (SERMs) has not been determined. Here we show that AIB1-Delta3 causes a significant increase in the efficacy of 17beta-estradiol at both estrogen receptor-alpha (ER-alpha) and ER-beta in ovarian, breast and endometrial cancer cell lines. AIB1-Delta3 also significantly increased the efficacy of the natural estrogen genistein at both ER-alpha and ER-beta, whereas AIB1 had no effect on either the potency or efficacy of genistein at either receptor. The estrogenic efficacy of the partial agonist tamoxifen was significantly increased in all cell lines at ER-alpha by overexpression of AIB1-Delta3 both on transfected and endogenous estrogen responsive genes. In contrast, overexpression of AIB1 or AIB1-Delta3 had no effect on the potency or efficacy of the SERM raloxifene. We conclude that overexpression of the AIB1-Delta3 isoform will increase the estrogenicity of a variety of natural and pharmacologic compounds in tissues that develop hormone-dependent neoplasias and overexpression of these cofactors may be a contributing factor to the hormone-driven development of neoplasia and to antiestrogen resistance of breast cancers.
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PMID:Impact of the nuclear receptor coactivator AIB1 isoform AIB1-Delta3 on estrogenic ligands with different intrinsic activity. 1469 61

The temporal and tissue-specific actions of estrogen are mediated by estrogen receptors alpha and beta. The ERs are steroid hormone receptors that modulate the transcription of target genes when bound to ligand. The activity of these transcription factors is regulated by a variety of factors, including ligand binding, phosphorylation, coregulators, and the effector pathway (ERE, AP1, SP1). The end result of target gene transcription is to modulate physiological processes, such as reproductive organ development and function, bone density, and unfortunately contribute to the growth and development of breast and endometrial cancer. The complex biological effects mediated by ER alpha and ER beta involve communication between many proteins and signaling pathways. An ultimate goal of current research is to enhance the value of the separate estrogen receptors as targets for therapeutic intervention.
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PMID:The biological role of estrogen receptors alpha and beta in cancer. 1509 56

Estrogen receptor (ER)-beta may play a significant role in estrogen action in several human tissues. Estrogen receptor beta may act as a transdominant repressor of ER alpha transcriptional activity trough heterodimers form. Estrogen receptor messenger RNA (mRNA) variants also may be involved in various diseases, including endometrial cancer. The absence of estrogen receptors has often correlated with poor prognosis of endometrial tumors. The objective of the study was to determine the number of mRNA ER beta delta 6 and (wtER beta) in 1 microgram total RNA obtained from tissues of normal, hyperplastic endometrium, and endometrial adenocarcinoma. This study was designed to evaluate possible differences in the ER beta delta 6 and wtER beta messenger RNA (mRNA) level in the normal, hyperplastic endometrium, and endometrial endometrioid adenocarcinoma (G1, G2 morphological degree). Adenocarcinoma showed significantly lower ER beta delta 6 mRNA level than proliferative (p = 0.032) and secretory (p = 0.01) endometrium. A decrease of mRNA wtER beta in endometrial adenocarcinoma (p = 0.006) also was observed.
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PMID:Estrogen receptor beta delta 6 (ER beta delta 6) isoform in human endometrial hyperplasia and adenocarcinoma. 1519 3

Although hormone replacement therapy (HRT) is used by post-menopausal women for the relief of menopausal symptoms and the potential reduction of osteoporosis, HRT also increases their risk of Alzheimer's disease, stroke, breast cancer, and endometrial cancer. Since the majority of these effects are associated primarily with estrogen binding to only one of the estrogen receptors (ER), new assays are needed that can more efficiently evaluate ER-binding and identify ligands selective for ER-alpha and ER-beta. High performance liquid chromatography-tandem mass spectrometry (LC-MS-MS) was combined with ultrafiltration as a new method to investigate the relative binding of compounds to the ERs and to evaluate the structures of these estrogens. Mixtures of estradiol and six equine estrogens, including equilin, equilenin, 8,9-dehydroestrone, and their 17beta-hydroxyl derivatives, were assayed simultaneously to determine their relative binding to human ER-alpha and ER-beta. Estrogens containing a 17beta-OH group were found to have higher relative affinities for the estrogen receptors than their ketone analogs. In addition, 17beta-EN showed selectivity for binding to ER-beta over ER-alpha. The results were compared to the IC50 values obtained by using a conventional radiolabled estradiol competitive binding assay. Finally, the utility of negative ion electrospray tandem mass spectrometry for the unambiguous identification of these estrogen isomers was investigated. Several characteristic recyclization pathways during tandem mass spectrometry were identified, which might be useful for distinguishing related estrogens.
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PMID:Ultrafiltration tandem mass spectrometry of estrogens for characterization of structure and affinity for human estrogen receptors. 1569 77

Information on the regulation of steroid hormone receptors and their distinct functions within the human endometrial epithelium is largely unavailable. We have immortalized human primary endometrial epithelial cells (EECs) isolated from a normal proliferative phase endometrium by stably transfecting the catalytic subunit (hTERT) of the human telomerase complex and cultured these hTERT-EECs now for over 350 population doublings. Active hTERT was detected in hTERT-EECs employing the telomerase repeat amplification assay protocol. hTERT-EECs revealed a polarized, non-invasive epithelial phenotype with apical microvilli and production of a basal lamina when grown on a three-dimensional collagen-fibroblast lattice. Employing atomic force microscopy, living hTERT-EECs were shown to produce extracellular matrix (ECM) components and ECM secretion was modified by estrogen and progesterone (P4). hTERT-EECs expressed inducible and functional endogenous estrogen receptor-alpha (ER-alpha) as demonstrated by estrogen response element reporter assays and induction of P4 receptor (PR). P4 treatment down-regulated PR expression, induced MUC-1 gene activity and resulted in increased ER-beta transcriptional activity. Gene activities of cytokines and their receptors interleukin (IL)-6, leukemia inhibitory factor (LIF), IL-11 and IL-6 receptor (IL6-R), LIF receptor and gp130 relevant to implantation revealed a 17 beta-estradiol (E2)-mediated up-regulation of IL-6 and an E2- and P4-mediated up-regulation of IL6-R in hTERT-EECs. Thus, hTERT-EECs may be regarded as a novel in vitro model to investigate the role of human EECs in steroid hormone-dependent normal physiology and pathologies, including implantation failure, endometriosis and endometrial cancer.
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PMID:Regulation of functional steroid receptors and ligand-induced responses in telomerase-immortalized human endometrial epithelial cells. 1582 Nov 14

This study was performed to examine the relationship between the anti-tumor effects of herbal medicine and endometrial carcinoma with ER-related mechanisms. An endometrial cancer cell line (Ishikawa) was used for this study. The cell viability and expression of estrogen receptors (ER) were determined by MTT and RT-PCR. A dose-dependent decrease of viability and apoptosis of the cancer cells was generated by exposure to the herbal medicines, Juzen-taiho-to or Shimotsu-to. The expression of ER-alpha mRNA, but not ER-beta mRNA was suppressed by Juzen-taiho-to or Shimotsu-to in an endometrial cancer cell line. The anti-tumor effect of these herbal medicines against endometrial carcinoma might be correlated to the ER-alpha related mechanism.
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PMID:Anti-tumor effects of herbal medicines on endometrial carcinomas via estrogen receptor-alpha-related mechanism. 1659 74

Endometrial cancer cell lines have provided a valuable model to study endometrial epithelial cells in vitro. Since the first development of HEC1B over 35 yr ago, many different cell lines have been isolated and described. One valuable cell line that maintains hormone responsiveness and unique stability over time is the ECC-1 cell line, developed originally by the late P.G. Satyaswaroop. In this study, we investigated some of the properties of these cells and present their salient characteristics. Like Ishikawa cells, ECC-1 cells maintain both estrogen receptors (ESR1 [ER alpha] and ESR2 [ER beta]), progesterone receptors (PR A and B; PGRs), and androgen receptors (ARs), along with the p160 steroid receptor coactivators NCOA1 (formerly SRC1), NCOA2 (formerly TIF2), and NCOA3 (formerly AIB1). The karyotype of these cells is abnormal, with multiple structural rearrangements in all cells analyzed. Unlike Ishikawa cells that express glandular epithelial antigens, ECC-1 cells maintain a luminal phenotype, with expression of KRT13 (cytokeratin 13) and KRT18 (cytokeratin 18). Apparent differences in the regulation of ESR2 also were evident in ECC-1 cells compared to Ishikawa cells. Like other endometrial cell lines, ECC-1 cells express the steroid receptor coactivators and exhibit epidermal growth factor-stimulated expression of known luminal proteins thought to be involved in implantation, including the hyaluronate receptor CD44 and SPP1 (formerly osteopontin) and CD55 (decay-accelerating factor). These characteristics appear to be stable and persistent over multiple cell passages, making this well-differentiated cell line an excellent choice to study endocrine and paracrine regulation of endometrial epithelium in vitro.
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PMID:ECC-1 cells: a well-differentiated steroid-responsive endometrial cell line with characteristics of luminal epithelium. 1670 68

An evaluation of the effects of a traditional Chinese herbal medicine, Hochu-ekki-to (Bu-zong-yi-qi-tang) on endometrial carcinogenesis was performed in experiments with female mice. In the short-term experiment, dietary exposure of Hochu-ekki-to (0.2% for 2 weeks) decreased the estradiol-17beta (E2)-stimulated expression levels of c-jun (P<0.001), tumor necrosis factor (TNF)-alpha (P<0.005), estrogen receptors (ER)-alpha (P<0.001) and ER-beta (P<0.005), as determined by reverse transcription-polymerase chain reaction and a Southern blot analysis in the uteri of the ovarectomized mice. In the long-term experiment, the mice were given N-methyl-N-nitrosourea (MNU) solution (1 mg/100 g body weight) and normal saline (as controls) into their left and right uterine corpora, respectively, and then were divided into four groups. Group 1 (25 mice) was given a diet with Hochu-ekki-to and 5 ppm E2. Group 2 (25 mice) was given a diet with E2 alone. Group 3 (25 mice) was given a diet with Hochu-ekki-to alone. Group 4 (25 mice) was kept on the basal diet alone and treated as a control. The incidence of uterine endometrial cancer in the group with Hochu-ekki-to treatment was substantially lower than of the control group. The inhibitory effect of Hochu-ekki-to on endometrial carcinogenesis is thus suggested to decrease the expressions of c-jun, TNF-alpha, ER-alpha and -beta.
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PMID:Inhibitory effects of Hochu-ekki-to on endometrial carcinogenesis induced by N-methyl-N-nitrosourea and 17beta-estradiol in mice. 1708 59

Estrogen receptor beta (ERbeta) has five carboxyl-terminal (C-terminal) isoforms derived from alternative splicing. ERbeta1 is the wild-type receptor whereas ERbeta2/betacx lacks the activation function (AF)-2 core essential for ligand-dependent transcriptional activation and so behaves as a dominant-negative receptor affecting the function of ERalpha. The objective of this study was to analyze the expression of ERbeta1 and ERbeta2/betacx isoforms in nonneoplastic endometrium and endometrioid carcinoma. The study was conducted on samples of 22 proliferative endometrium, 15 secretory endometrium, 20 simple hyperplasia (without atypia), and 26 endometrioid carcinomas. The transcript and protein levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. For the detection of ERbeta2/betacx protein, a polyclonal antibody was raised to its unique C-terminus, characterized, and used in immunohistochemistry. The two ERbeta isoforms are expressed in the proliferative and secretory phase endometrium with no significant change in their relative levels. The levels of the ERbeta1 isoform were lower as compared to the levels of ERbeta2 in all the groups studied. Expression of ERbeta2/betacx was decreased in endometrioid carcinoma as compared to proliferative endometrium (P < 0.01). A significant decrease of the ERbeta2/ERbetacx transcript was observed with higher grade tumors (P = 0.041). Progesterone receptor (PR) expression was not influenced by either of the ERbeta isoforms which was observed by logistic regression analysis in all the groups. The coexpression of ERbeta2/betacx with ERalpha did not affect PR levels (logistic regression analysis). Thus, we conclude in the human endometrium, there is significant ERbeta2/betacx isoform expression and alterations in its levels could be involved in endometrial cancer progression.
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PMID:Estrogen receptor beta1 and the beta2/betacx isoforms in nonneoplastic endometrium and in endometrioid carcinoma. 1730 72

The objectives were to study the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) and estrogen receptor (ER) subtypes in the normal, hyperplastic, and carcinomatous endometrium and to explore their possible role in carcinogenesis and progression of endometrial carcinoma. Immunohistochemistry and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) were applied to detect protein and messenger RNA expression of RCAS1, ER-alpha, and ER-beta in normal, hyperplastic, and carcinomatous endometrium. Western blotting was also used to detect the RCAS1 protein expression. Immunohistochemistry showed that the high expressions of RCAS1 protein were 0% (0/20), 9.1% (2/22), 40% (8/20), and 68.0% (34/50) in normal, simple, and complex hyperplasia, atypical hyperplasia, and endometrial carcinoma, respectively. There was a significant difference between each group (P < 0.05). The high-level expression of RCAS1 was detected more frequently in endometrial cancer with deep myometrial invasion, vascular invasion, and positive ER-alpha (P < 0.05). Two staining patterns of RCAS1 were observed. All normal, simple, and complex hyperplastic endometrium showed P pattern, while all malignant endometrium were of the D pattern. In atypical endometrium, 25% (5/20) cases showed D pattern. The Western blotting and RT-PCR results correlated with the immunohistochemistry results. The expression and distribution of RCAS1 may be involved in the malignant transformation of endometrium, and RCAS1 coexpression with ER-alpha may be associated with development and metastasis of endometrial carcinoma.
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PMID:Expression of receptor-binding cancer antigen expressed on SiSo cells and estrogen receptor subtypes in the normal, hyperplastic, and carcinomatous endometrium. 1746 50


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