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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this paper we report that two human long-term endometrial cancer cell lines, Ishikawa and HEC-1A, exhibit quite different abilities in metabolizing estrogens. As a matter of fact, incubation of Ishikawa cells with close-to-physiological concentrations of estradiol (E2) as precursor resulted in: (1) elevated formation (up to 90%) of E2-sulphate (E2-S), using lower precursor concentrations; (2) very limited conversion to estrone (E1) (< 10% at 24 h incubation), as either free or sulphate; and (3) low but consistent production of other estrogen derivatives, such as 2-hydroxy-estrogens and estriol. Conversely, scant amounts (if any) of E2-S were found in HEC-1A cells, while no detectable formation of other estrogen metabolites could be observed after 24 h. On the other hand, E1 production was significantly greater (nearly 60% at 24 h) than in Ishikawa cells, a large proportion of E1 (over 50% of the total) being formed after only 6 h incubation using time-course experiments. The hypothesis that E2 metabolism could be minor in Ishikawa cells as a consequence of the high rate of E2-S formation encountered is contradicted by the evidence that conversion to E1 also remains limited in the presence of much lower E2-S amounts, seen using higher molar concentrations of precursor. Overall, we observe that 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity diverges significantly in intact Ishikawa and HEC-1A endometrial cancer cells. This difference could not merely be accounted for by the diverse amounts of substrate (E2) available to the cells, nor may it be imputed to different levels of endogenous estrogens. It should rather be sought in different mechanisms controlling 17 beta-HSD activity or, alternatively, in the presence of distinct isoenzymes in the two different cell types.
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PMID:17 beta-Hydroxysteroid dehydrogenase activity in endometrial cancer cells: different metabolic pathways of estradiol in hormone-responsive and non-responsive intact cells. 854 84

The presence of a direct extra-pituitary action of gonadotropin-releasing hormone (GnRH) via specific receptors in endometrial cancer (EC) has been suggested as an explanation for the therapeutic effect of GnRH analogue (GnRHa) in recurrent disease. We have sought the expression of the GnRH peptide and functional GnRH receptor (GnRH-R) in human tissues and cell lines to investigate the possibility of an autocrine growth regulation mechanism. Using reverse transcription-PCR, differing GnRH mRNA transcripts were detected in two EC cell lines (Ishikawa and HEC-1A), a choriocarcinoma (JEG3) cell line, and tissues from endometrium and placenta. However, secretion of immunoreactive GnRH could be detected by RIA in only 1 of 10 EC tissues in primary culture, and in none of the cell lines. Low levels of GnRH-R mRNA expression were found in the same cells, which were only detectable by reverse transcription-PCR and Southern blotting of the PCR product. In radioligand binding assays using GnRHa goserelin, no pituitary-like, high-affinity GnRH binding sites could be found in either EC cell lines or tissues. Low affinity binding (Kd = 1.0 - 3.1 x 10(-7)M) was detected in three of eight (37%) EC tissues. Furthermore, receptor signal transduction measurements carried out in these cells showed no increases in either total inositol phosphate, cyclic AMP production, or cytosolic Ca2+ in response to either GnRH or GnRHa. Finally, no effect of either GnRH or GnRHa on the growth of EC cell lines was detected in vitro, under estrogen-free conditions, assessed by DNA content. Our data suggest that although there is a potential for autocrine activity for GnRH in EC as judged by the presence of mRNA for peptide and receptor, no functional receptor activity could be detected in vitro. Alternative mechanisms should be studied to explain the in vitro action of GnRHa.
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PMID:The expression of gonadotropin-releasing hormone and its receptor in endometrial cancer, and its relevance as an autocrine growth factor. 861 51

Invasiveness of endometrial cancer cells such as Ishikawa, HEC-1-A and HHUA cells, to the interstitium was significantly enhanced by estradiol, while medroxyprogesterone acetate (MPA) significantly diminished the estradiol-enhanced invasive potential. All of these endometrial cancer cells possess estrogen receptors. It is suggested that invasiveness to the interstitium, and consequently infiltration to the uterine myometrium (which means local advance) are activated by estradiol via a mechanism related to the estrogen receptor, and that MPA as an antiestrogen agent partly inactivates the invasive ability.
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PMID:Estrogen activates invasiveness of endometrial cancel cells to the interstitium. 862 Dec 69

The human estrogen receptor (ER) is a ligand-inducible transcription factor that contains two transcriptional activation functions, one located in the NH2-terminal region of the protein (AF-1) and the second in the COOH-terminal region (AF-2). Antiestrogens, such as trans-hydroxytamoxifen (TOT), have partial agonistic activity in certain cell types, and studies have implied that this agonism is AF-1-dependent. We have made progressive NH2-terminal and other segment deletions and ligations in the A/B domain, and studied the transcriptional activity of these mutant ERs in ER-negative MDA-MB-231 human breast cancer and HEC-1 human endometrial cancer cells. Using several estrogens and several partial agonist/antagonist antiestrogens, we find that estrogens and antiestrogens require different regions of AF-1 for transcriptional activation. Deletion of the first 40 amino acids has no effect on receptor activity. Antiestrogen agonism is lost upon deletion to amino acid 87, while estrogen agonism is not lost until deletions progress to amino acid 109. Antiestrogen agonism has been further defined to require amino acids 41-64, as deletion of only these amino acids results in an ER that exhibits 100% activity with E2, but no longer shows an agonist response to TOT. With A/B-modified receptors in which antiestrogens lose their agonistic activity, the antiestrogens then function as pure estrogen antagonists. Our studies show that in these cellular contexts, hormone-dependent transcription utilizes a range of the amino acid sequence within the A/B domain. Furthermore, the agonist/antagonist balance and activity of antiestrogens such as TOT are determined by specific sequences within the A/B domain and thus may be influenced by differences in levels of specific factors that interact with these regions of the ER.
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PMID:Different regions in activation function-1 of the human estrogen receptor required for antiestrogen- and estradiol-dependent transcription activation. 879 58

The observation that charcoal-treated fetal bovine serum (ctFBS) was able to modify one of main pathways of estrogens in cancer cells in culture, prompted us to initiate the present study. The active component of serum was isolated using native preparative polyacrylamide gel electrophoresis (PAGE). Under analysis with SDS-PAGE, a M(W) of 68 kDa and mobility of authentic bovine serum albumin (BSA) was observed. The addition of BSA to the serum free culture medium of HEC 1A human endometrial cancer cell line, resulted in an alteration of estradiol (E2) metabolism similar to that observed in the presence of ctFBS. BSA in fact, much enhanced 16 alpha-hydroxylation and significantly reduced 2-hydroxylation of E2 in HEC 1A cells. Comparable results were obtained with different endometrial (Ishikawa) and mammary (MCF-7) tumor cell lines having a different metabolic conversion rate of E2. Several albumin preparations from either bovine or human serum had the same effect; besides, BSA activity was unaffected by treatment with dextran-charcoal or heat. In the light of the present results, the inclusion of serum albumin (SA) in the formulation of media for studies evaluating steroid metabolism in cultured cells should be carefully considered.
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PMID:Effect of serum albumin on estrogen metabolism in human cancer cell lines. 882 98

The enhancement of the in vitro invasive ability and the morphological changes caused by anti-E-cadherin antibody HECD-1 were investigated by in vitro invasion assay and electron microscopy in three human endometrial carcinoma cell lines. The cell lines were NUE-1 (E-cadherin negative and high in vitro invasive ability), HEC-1BE and HEC-108 (E-cadherin positive and low in vitro invasive ability). In NUE-1 invasive ability was not enhanced by HECD-1, but in HEC-1BE and HEC-108 invasive ability was enhanced to 223 +/- 41.2% and 307 +/- 173% by 5 micrograms/ml HECD-1. Morphologically NUE-1 invaded the extracellular matrix (Matrigel) with a long micro villis. But in HEC-1BE and HEC-108 the villis did not invade the Matrigel, the whole cell invaded it. Together with HECD-1, HEC-1BE and HEC-108 were changed to become similar to the NUE-1 cell line with high invasive ability and the micro villis invaded the Matrigel.
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PMID:[Experimental studies on the cell adhesion molecule E-cadherin and in vitro invasion of endometrial carcinoma cell lines]. 884 59

This paper summarizes our most recent results of steroid enzyme studies on cultured breast and endometrial cancer cells. It deals mainly with estrogen 17 beta-hydroxysteroid oxidoreductase (17 beta HSOR) activity, which presides over estradiol (E2) and estrone (E1) interconversion, a major metabolic pathway of estrogens. Assessment of either the oxidative or reductive component of 17 beta HSOR was carried out on intact cells by means of an original approach based on reverse phase-high performance liquid chromatography and radioactive detection on line. This system allows the continuous monitoring of both precursor degradation and formation of several radiometabolites to assess rates and direction of steroid metabolism. Overall, hormone-responsive, estrogen receptor (ER)-positive cells, regardless of whether they were derived from breast (MCF7) or endometrial (Ishikawa) tumor tissues, showed a prevalence for reductive metabolism (E1-->E2), whilst oxidative pathways (E2-->E1) were largely dominant in non-responsive, ER-poor mammary (MDA-MB231) and endometrial (HEC-1A) cells. The above estimates of 17 beta HSOR activity were at variance with those obtained using the classical enzymology approach, not only in quantitative terms (being markedly lower using intact cell analysis), but also because the prevalent direction of estrogen metabolism was often reversed. Although striking methodological differences may well account for this discrepancy, intact cell analysis is undoubtedly more similar to the in vivo state than the artificial requirements of classical enzymology procedures.
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PMID:17 beta-hydroxysteroid oxidoreductase activity in intact cells significantly differs from classical enzymology analysis. 894 90

Wnt genes are transforming to mouse breast epithelium and are hormonally regulated in vivo. To assess their role in another endocrine-responsive human cancer, the expression of seven Wnt genes (Wnt 2, 3, 4, 5a, 7a, 7b and 10b) in normal human endometrium and endometrial cells, and endometrial carcinoma tissues and cell lines was investigated by ribonuclease protection analysis. Wnt2, 3, 4 and 5a mRNAs but not Wnt7a, 7b or 10b mRNAs were expressed in primary culture of normal endometrial epithelial (NEE) and stromal (NES) cells. In contrast, in four endometrial carcinoma cell lines (RL95-2, HEC-1-A, AN3 CA and Ishikawa), Wnt2 and Wnt3 mRNAs were absent. Wnt4 was expressed in only one out of four cell lines (RL95-2), and Wnt5a was much lower. Wnt7a and Wnt7b mRNAs were expressed in three out of four cell lines (RL95-2, HEC-1-A and Ishikawa). Wnt10b mRNA was expressed in RL95-2 and AN3 CA. In fresh tissues, all Wnt genes apart from Wnt10b were expressed in normal endometrium and endometrial carcinoma. Similar to the cell lines, the level of Wnt4 mRNA expression was significantly higher in the normal endometrium than endometrial carcinoma. Wnt2, 3 and 5a mRNAs were also lower in endometrial carcinoma compared with normal endometrium. There was no difference in the level of Wnt2, 3, 4 and 5a mRNA expression between proliferative phase and secretory phase of the menstrual cycle, or between either menstrual phase and the first trimester of pregnancy. In vitro, progesterone and/or 17beta-oestradiol had no effect on Wnt2, 3, 4, 5a and 7b mRNA expression in NES and all endometrial carcinoma cell lines. The data indicate that all Wnt genes were expressed in vitro, six out of seven Wnt genes (Wnt 2, 3, 4, 5a, 7a and 7b) were expressed endogenously in the human endometrium, their mRNA expression was hormonally independent and Wnt4 gene down-regulation as well as down-regulation of Wnt 2, 3 and 5a may be associated with endometrial carcinoma.
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PMID:Expression and hormone regulation of Wnt2, 3, 4, 5a, 7a, 7b and 10b in normal human endometrium and endometrial carcinoma. 909 60

Growth factor regulation of normal and cancerous cell proliferation has been well-documented and may be mediated by proto-oncogene activity. The purpose of this study was to assess changes in proliferation and mitogen-induced c-fos mRNA expression of an endometrial carcinoma cell line, HEC-1-A, in response to TGF-beta, a potent growth-inhibitory peptide. HEC-1-A cells were incubated in the presence or absence of TGF-beta. Mitogen-stimulated cells were additionally treated with epidermal growth factor (EGF). Changes in proliferation were measured by [3H]thymidine uptake assays. Alterations in EGF-induced c-fos expression following TGF-beta pretreatment were assessed by Northern blot using a 32P-labeled human c-fos probe. Finally, chloramphenicol acetyltransferase assays were performed to evaluate c-fos promoter activity in response to treatment conditions. Basal and EGF-stimulated proliferation was inhibited by TGF-beta in a dose- and time-dependent manner. TGF-beta also reversibly decreased EGF-induced c-fos mRNA expression in a dose- and time-dependent manner. Sequences in the c-fos promoter that were stimulated by EGF showed suppressed activity when preincubated with TGF-beta. These results show that TGF-beta negatively modulates EGF-induced c-fos expression, which may be related to the observed inhibition of carcinoma cell proliferation.
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PMID:Transforming growth factor-beta negatively modulates proliferation and c-fos expression of the human endometrial adenocarcinoma cell line HEC-1-A. 910 92

In vitro studies on endometrial carcinogenesis have been hampered by limited differentiation of the cells in culture. Using the endometrial carcinoma cell lines HEC 1B and its subclone HEC 1B(L), we established and characterized cell culture conditions that preserve a more differentiated state of the tumor cells. Randomly seeded HEC 1B(L) cells, if grown in a serum-free defined medium on top of a reconstituted basement membrane (Matrigel), within a few hours assembled themselves to web-like structures. In a thick layer of Matrigel, they showed an even more pronounced morphological differentiation. Functionally, two additional secretory proteins, about 31 and 77 kDa in size, became apparent as a response to matrigel. To further investigate the regulatory role of the extracellular matrix in the process of in vitro differentiation of endometrial adenocarcinoma cells, we addressed two specific problems. First, we investigated if the capacity of in vitro differentiation is a specific feature of HEC 1B(L) cells or if it is common to all endometrial adenocarcinoma cells. Second, we tried to identify the Matrigel component(s) responsible for in vitro differentiation. The assembly of HEC 1B and HEC 1B(L) cells into spatially organized web-like structures and the expression of the 77 kDa protein were thereby used as an assay. All endometrial adenocarcinoma cell lines tested to a variable degree formed web-like structures on Matrigel. Although the pattern of de novo synthesized secretory proteins changed as a response to Matrigel, only HEC 1A, HEC 1B, HEC 1B(L), and Ishikawa cells responded to culture on Matrigel by an increased expression of the 77 kDa protein. Functionally, polyclonal anti-laminin antibodies, but not anti-collagen type IV antibodies, disrupted formation of web-like structures by HEC 1B cells. The laminin-specific peptides YIGSR and SIKVAV but none of the RGD-peptides RGDS, GRGDSP, or GRADSP affected the three-dimensional assembly of these cells in vitro. Both anti-laminin antibodies and laminin-specific peptides suppressed Matrigel-induced formation of the 77-kDa secretory protein by HEC 1B cells. These findings suggest the involvement of laminin in the in vitro differentiation of the HEC 1B endometrial adenocarcinoma cell line. In a mechanistic view, laminin appears to play a crucial role in the regulation of this in vitro differentiation process.
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PMID:Laminin mediates basement membrane induced differentiation of HEC 1B endometrial adenocarcinoma cells. 916 56


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