UMLS:C0476089 - FACTA Search

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

Local invasiveness is an important prognostic factor in endometrial carcinoma. To study the role of two groups of secreted proteinases (serine proteinases and matrix metalloproteinases) in this process, we examined three endometrial cancer cell lines (Ishikawa HEC 1A, AN3CA) for their invasiveness in vitro. Additionally, we considered the secretion of urokinase type plasminogen activator (uPA), plasminogen activator inhibitor 1 and 2 (PAI-1 and PAI-2), as well as matrix metalloproteinases (MMP) 1, 2, 3, and 9, and their inhibitors TIMP-1 and TIMP-2. Compared to the highly invasive fibrosarcoma cell line HT 1080, Ishikawa displayed low and AN3CA moderate invasiveness, while HEC 1A cells were almost as invasive as HT 1080 cells. Ishikawa cells secreted the highest amounts of proteinases. Cytokine and steroid treatments upregulated MMP-1 in all cell lines while the effects were heterogeneous regarding other proteinases and inhibitors. No effect of these treatments on invasiveness could be detected. Both basal secretion and regulation of the proteinases tested in this set of experiments seem to be markers of differentiation rather than of invasiveness.
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PMID:Invasiveness corresponds to differentiation rather than to proteinase secretion in endometrial cancer cell lines. 1060 96

Basic transcription element binding (BTEB, also designated BTEB1) protein is a member of the Sp-family of GC-box binding transcription factors that exhibit distinct patterns of expression in many cell types and tissues. A role for BTEB1 in the regulation of cell growth and gene transcription has been invoked, but little is known about the molecular mechanisms underlying these activities. The present study examined the functional consequences of high and low BTEB1 expression in the human endometrial carcinoma cell line Hec-1-A, by deriving stable clonal lines that expressed sense (S) and anti-sense (As) rat BTEB1 constructs. Clonal S lines, with BTEB1 mRNA and protein levels higher than in corresponding parent (N) and As lines, displayed enhanced DNA synthesis upon 3[H]-thymidine incorporation, in serum-containing but not in serum-free medium, and increased cell cycle kinetics, concomitant with the induction in expression of the genes for the cell cycle-associated components cyclin D1, PCNA, cyclin-dependent kinase (Cdk) inhibitor p21, and Cdk2. Compared to N and As lines, S lines also had diminished ability to grow in multi-layers and exhibited increased mRNA levels for plasminogen activator inhibitor-1 (PAI-1), secretory leukocyte protease inhibitor (SLPI), and tissue inhibitor of metalloproteinases (TIMP)-2. In serum-free medium, S, but not N nor As lines, had enhanced DNA synthesis with transforming growth factor (TGF)-beta1, albeit all lines demonstrated similar responses to insulin-like growth factor-I and to epidermal growth factor, respectively. The higher DNA synthesis in S relative to N and As, lines upon exogenous TGF-beta1 addition, was observed in concert with increased expression of cyclins D1 and E and p21, genes. Moreover, S and As lines had increased mRNA levels for TIMP-1, TIMP-2, PAI-1, and beta-catenin, and diminished SLPI, and to a lesser extent, Cdk4 mRNA levels, with TGF-beta1 treatment. These results suggest that BTEB1 may mediate cell growth, in part, by modulating gene expression levels of distinct cell cycle and growth-associated proteins. The correlation between serum- and TGF-beta1 induction of DNA synthesis with increased BTEB1 expression further suggests that BTEB1 may constitute an important downstream regulatory component of various signaling pathways utilized by serum-associated and other growth factors in endometrial epithelial cells.
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PMID:Increased expression of the Zn-finger transcription factor BTEB1 in human endometrial cells is correlated with distinct cell phenotype, gene expression patterns, and proliferative responsiveness to serum and TGF-beta1. 1147 43

Matrix metalloproteinase (MMP)-2 and -9 are secreted and translocated from endometrial stromal cells to HEC-1 A cells in a steroid-dependent manner. We investigated the paracrine effect of hepatocyte growth factor (HGF) on MMPs and metalloproteinase tissue inhibitor (TIMP) expression in stromal and endometrial cancer cells, and correlated with cancer cell invasiveness in three-dimensional (3D) coculture. The 3D coculture of endometrial stromal and cancer cell lines (HEC-1 A, HEC-IB, or KLE) were maintained in the presence or absence of HGF. The expression of MMP-2 and -9, MT1-MMP, TIMP-1 and -2 were examined by RT-PCR and zymography. Under the same conditions, invasion of the cancer cells was quantified by Boyden's chamber assay. HGF strongly induced MMP-9 mRNA expression in stromal cells, but had little effect on MMP-2 mRNA. MT1-MMP mRNA was detected only in KLE and stromal cells, which was also increased by HGF. TIMP-1 and -2 mRNAs was ubiquitous with no dependence on HGF. Zymographic analysis of MMPs showed that activation of MMP-2 and -9 was enhanced by HGF. A significant increase in invasion of all three cancer cells with HGF was observed. The effect of HGF on the invasiveness of 3D cocultured endometrial cancer cells and stromal cells appears to be due to induction of MMP-9 mRNA expression in stromal cells and /or increased activation of MMP-2 and MMP-9 by proteolytic digestion.
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PMID:Effects of hepatocyte growth factor on the expression of matrix metalloproteinases and their tissue inhibitors during the endometrial cancer invasion in a three-dimensional coculture. 1263 Dec 21

Steroid hormones regulate endometrial expression of matrix metalloproteinases (MMPs) and their inhibitors. Synthetic progestins are widely used in oral contraceptives and for hormone replacement therapy. To assess whether the synthetic progestins norgestimate and its derivative norelgestromin (17-deacetylnorgestimate) modulate the expression of MMPs, Ishikawa endometrial cancer cells were separately treated with 17 beta-estradiol, 17 alpha-hydroxyprogesterone, norgestimate and norelgestromin. Culture supernatants were assayed for MMPs 2, 3 and 9, and for tissue inhibitors of MMPs (TIMP-1 and TIMP-2) by enzyme-linked immunosorbent assays (ELISAs). No marked modulation of MMP-2 and TIMP-2 expression was observed upon incubation of the cells with the synthetic progestins. By ELISA, neither MMP-3 or MMP-9 nor TIMP-1 immunoreactivity was detected. Interestingly, TIMP-2 expression was down-regulated by 17 beta-estradiol and 17 alpha-hydroxyprogesterone.
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PMID:Matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 expression is not regulated by norgestimate or norelgestromin. 1510 61

Matrix metalloproteinases (MMPs) are associated with invasion and metastasis of several human malignant tumors, in particular MMP-7, which is mainly produced by the cancer cell itself. We examined the expression of MMP-2, 7 and 9, and tissue inhibitors of metalloproteinase (TIMP)-1 and 2 in uterine endometrial carcinoma, and compared the expression with clinicopathological characteristics in uterine endometrial carcinoma (UEC). A group of 256 patients with UEC received surgery at the Osaka City University Medical School Hospital, and 196 tumor samples were immunohistochemically stained to examine the expression of MMP-2, 7 and 9, and TIMP-1 and 2. Additionally, the invasion ability of cell stain established from UEC was examined using an in vitro invasion assay. The expression of MMP-2, 7 and 9, and TIMP-1 and 2 was observed in the cytoplasm, and the expression of MMP-2 and 7, and TIMP-1 and 2 was observed in stromal cells around the tumor cells. The expression of MMP-7 was significantly stronger in higher-grade than lower-grade tumors (P<0.05). The invasion assay showed that the invasion of cells derived from UECs was significantly inhibited by TIMP-1 and 2. The disease-free interval was significantly shorter when MMP-7 expression was intense. This increased expression of MMP-7 in high grade UECs may be associated with tumor invasion and metastasis, and MMP-7 could serve as a prognostic maker in UEC.
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PMID:Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in uterine endometrial carcinoma and a correlation between expression of matrix metalloproteinase-7 and prognosis. 1614 84

Endometrioid endometrial carcinoma developed from endometrial hyperplasia is associated with anomalies of proliferation, apoptosis, and matrix metalloproteinase (MMP) expression. Our study was designed to investigate steroid receptor (ER, PR) expression and its correlation with proliferative activity (PCNA), apoptosis (Fas, FasL, Bcl-2, Bax, and p53), gelatinases (MMP-2 and MMP-9) and their tissue specific inhibitor (TIMP-1 and TIMP-2) immunoexpression in endometrial carcinogenesis. A total of 38 cases were investigated, 10 non-neoplastic, 11 hyperplastic, and 17 carcinomatous endometria. Immunolabeling showed a higher expression of steroid receptors in hyperplasia and carcinoma than in non-neoplastic endometria and an ER/PR imbalance in carcinoma. The epithelial component of endometrial carcinomas had the highest proliferative index. Bcl-2 had a stronger expression in hyperplasia and carcinoma compared to non-neoplastic endometria and stromal tissue. The Bcl-2/Bax ratio was lower in endometrial carcinoma. Fas and FasL expression was stronger in hyperplasia and furthermore in carcinoma. p53 expression was progressively stronger along the sequence non-neoplastic endometrial to hyperplasia-carcinoma. Both types of investigated MMPs showed an increased expression in neoplastic endometria reaching a maximum level in carcinomas. MMP-9 immunostaining could be correlated to myometrial invasion. TIMP-1 decreased and TIMP-2 increased in expression from non-neoplastic endometria to hyperplastic and carcinomatous endometrial, respectively. Our study demonstrates that coordinated anomalies of steroid receptors, apoptosis and invasiveness factors are already present in hyperplasia as cumulative steps along the way to malignant transformation and that a complex MMP-2, MMP-9, TIMP-2/TIMP-1 imbalance seems to be responsible for the endometrial proliferation.
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PMID:Immunohistochemical analysis of steroid receptors, proliferation markers, apoptosis related molecules, and gelatinases in non-neoplastic and neoplastic endometrium. 2114 16

The role of hyaluronan (HA), serum-derived HA-associated protein (SHAP)-HA complex and hyaluronan synthase (HAS) in endometrial carcinomas was investigated. The relationship of metalloproteinase (MMP) and its inhibitor (TIMP) with HA and the SHAP-HA complex was also examined. The expression of HAS1 was related to the depth of myometrial invasion and lymph-vascular space involvement. The serum levels of HA, SHAP-HA complex, MMP-9, and TIMP-1 were increased in related with the depth of myometrial invasion, histological grade and lymph-vascular space involvement. They were also higher in the HAS1-positive group compared to -negative group. The serum concentrations of HA and SHAP-HA complex had a significant correlation with the MMP-9 and TIMP-1. The patients with elevated SHAP-HA complex had the shorter disease-free survival. The multivariate analysis revealed that the SHAP-HA complex was the independent variable for disease-free survival of endometrial cancer patients. In conclusion, the elevation of serum SHAP-HA complex depended on the HAS1 expression and the SHAP-HA complex is a useful marker to predict disease recurrence in endometrial cancer patients. The SHAP-HA complex may promote the lymph-vascular space involvement and the synthesis and activation of MMP-9 and TIMP-1 in the progression of endometrial cancer.
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PMID:Clinicopathological Role of Serum-Derived Hyaluronan-Associated Protein (SHAP)-Hyaluronan Complex in Endometrial Cancer. 2190 55

Tissue inhibitors of metalloproteinases are important regulators of metalloproteinase activity, and the balance of active enzyme and inhibitor is a critical determinant of tumor cell invasiveness. This study aimed to evaluate the prognostic and clinical implications of the two main inhibitors of matrix metalloproteinases, TIMP-1 and TIMP-2, in endometrial carcinoma. The material consisted of 241 patients with primary endometrial carcinoma. The median follow-up time was 77 months. Expressions of TIMP-1 and TIMP-2 proteins were examined in paraffin-embedded tumor sections by immunohistochemical methods. Positive staining for TIMP-1 and -2 was observed in 88% and 86% of the primary tumors, respectively. The Kaplan-Meier analysis showed that the 5-year cancer-specific survival rate of the patients with TIMP-2 positive immunostaining was 89% and that of the TIMP-2 negative patients 78%. Positive immunoreaction for TIMP-2 correlated with favorable cancer-specific and overall survival. When including only endometrioid adenocarcinomas, a similar trend towards favorable survival was seen. Excluding stage IA carcinomas, the difference became again statistically significant. For TIMP-1, there was no statistically significant association with overall or cancer-specific survival. The Cox regression analysis showed stage, grade and TIMP-2 to be significant predictors of survival. We suggest that TIMP-2 may have a more important role in endometrial carcinoma progression than TIMP-1 and might serve as a potential marker for favorable prognosis in this type of cancer.
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PMID:Immunoreactivity for TIMP-2 is associated with a favorable prognosis in endometrial carcinoma. 2227 Apr 51

The risk of endometrial hyperplasia (EH) progressing into endometrioid endometrial cancer ranges from 1% for simple EH without atypia (EHWA) to 46.2% for atypical EH (AEH). Differentiation between both entities is crucial to determine optimal management. As preoperative diagnosis of AEH can be difficult, we aimed to establish clusters of immunohistochemical markers to distinguish EHWA from AEH. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins, metalloproteinases (MMP), tissue inhibitor of metalloproteinase (TIMP), CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating EHWA from AEH. From 39 tissue samples (17 EHWA and 22 AEH), we found three clusters of co-expressed proteins: Cluster 1 included two proteins (over-expression of estrogen receptor (ER) and under-expression of progesterone receptor (PR) B in AEH compared to EHWA); Cluster 2: an ER, PR A, MMP-2 and TIMP-1 over-expression and a PR B and TIMP-2 under-expression; Cluster 3: over-expression of ER and MMP-7 and under-expression of PR B and TIMP-2. AEH can be accurately distinguished from EHWA using a supervised clustering of immunohistochemical markers. This promising approach could be useful to improve the preoperative diagnosis of EH.
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PMID:Supervised clustering of immunohistochemical markers to distinguish atypical and non-atypical endometrial hyperplasia. 2549 49

The relationship between intake of fish and n-3 fatty acids and endometrial cancer risk has not been consistent across epidemiological studies. We quantitatively assessed the aforementioned association through a systematic review and meta-analysis. PubMed and Embase were searched through March 2017 for eligible epidemiological studies. Fixed or random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs). The dose-response relationship was also evaluated. Based on the literature search, five prospective studies and 11 case-control studies were identified. All 16 studies were categorized as high-quality studies. After pooling available risk estimates, no significant association was detected between overall fish intake and endometrial cancer risk. In subgroup analyses, every one additional serving/week of fish intake was significantly associated with inversed endometrial cancer risk in studies adjusted for smoking (RR (95% CI): 0.95 (0.91-1.00)), or studies performed in Europe (RR (95% CI): 0.90 (0.84-0.97)), but not in other tested subgroups. In studies conducted in Asia, there was significant positive association (RR (95% CI): 1.15 (1.10-1.21)). Regarding n-3 PUFA intake, marginally inverse associations of high EPA or DHA intake were detected (EPA: RR (95% CI) = 0.79 (0.61-1.04); DHA: RR (95% CI) = 0.85 (0.64-1.11)). Dose-response analyses suggested a significant nonlinear relationship between DHA intake and endometrial cancer risk (p: 0.04). Overall, this meta-analysis suggests that intake of n-3 PUFA may be inversely associated with endometrial cancer risk at some level of evidence, although the exact relationship, especially for fish intake, needs further characterization. Further well-designed studies are warranted.
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PMID:Dietary n-3 polyunsaturated fatty acids, fish consumption, and endometrial cancer risk: a meta-analysis of epidemiological studies. 2920 77

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