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

Tumor progression is often regulated through interactions between carcinoma cells and host stromal cells. In this study of endometrial cancer, we investigated one mechanism potentially involved in hepatocyte growth factor (HGF)-mediated cancer-stromal interactions. Endometrial cancer cells (HEC-1 and ISHIKAWA) expressed the c-met receptor, but HGF did not. HGF, however, did stimulate the proliferation and invasion of these cells. The HGF gene was expressed in stromal cells, which had been separated from primary cultures of endometrial cancers, 6.4 times more than in isolated normal endometrial stromal cells. Immunohistochemical staining revealed immunoreactive HGF in cancer stromal cells, the staining intensity being more pronounced in cancer tissue than in normal endometrium. The conditioned medium from normal epithelial cells and cancer cell lines induced HGF production in normal stromal cells. We identified basic fibroblast growth factor as an HGF inducer derived from endometrial cancer cell lines. Basic fibroblast growth factor derived from tumor cells may induce HGF in endometrial stromal cells, whereas stromal cell-derived HGF leads to the invasive growth of carcinoma cells. These interactions, mediated by HGF and HGF inducers, may play a significant role in the progression of endometrial cancer.
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PMID:Induction of hepatocyte growth factor in stromal cells by tumor-derived basic fibroblast growth factor enhances growth and invasion of endometrial cancer. 1199 90

It is well known that the functions of reproductive organs are regulated by sex steroids and their receptors and it is hypothesized that the progression of neoplasms that originate from the reproductive organs is influenced by them. However, the correlation between sex steroids and tumor progression, especially tumor invasion, is not well known in endometrial carcinoma. In our study, we focused on the influence of estrogen and its receptor in invasion and matrix metalloproteinases (MMPs), which are known to be important in tumor invasion, as well as on endometrial carcinoma cells. The growth of Ishikawa cells, to which an estrogen receptor-alpha expressing vector was transfected, was accelerated by 17 beta-estradiol as was the acceleration of the expression of cyclin D1. By invasion assay, in conditions with 17 beta-estradiol, the invasiveness of Ishikawa cells was enhanced. Furthermore, according to the accelerated invasiveness, the expression of MMP-1, -7 and -9 and Ets-1 was enhanced. These results suggest that activation of ER-alpha by estrogen results in tumor progression by stimulating cell growth and invasiveness via acceleration of the expression of MMPs.
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PMID:Acceleration of invasive activity via matrix metalloproteinases by transfection of the estrogen receptor-alpha gene in endometrial carcinoma cells. 1211 20

PTEN on 10q23.3 encodes a dual-specificity phosphatase that negatively regulates the phosphoinositol-3-kinase/Akt pathway and mediates cell-cycle arrest and apoptosis. Germline PTEN mutations cause Cowden syndrome and a range of several different hamartoma-tumor syndromes. Hereditary nonpolyposis colon cancer (HNPCC) syndrome is characterized by germline mutations in the mismatch repair (MMR) genes and by microsatellite instability (MSI) in component tumors. Although both colorectal carcinoma and endometrial carcinoma are the most frequent component cancers in HNPCC, only endometrial cancer has been shown to be a minor component of Cowden syndrome. We have demonstrated that somatic inactivation of PTEN is involved in both sporadic endometrial cancers and HNPCC-related endometrial cancers but with different mutational spectra and different relationships to MSI. In the current study, we sought to determine the relationship of PTEN mutation, 10q23 loss of heterozygosity, PTEN expression, and MSI status in colorectal cancers (CRCs). Among 11 HNPCC CRCs, 32 MSI+ sporadic cancers, and 39 MSI- tumors, loss of heterozygosity at 10q23.3 was found in 0%, 8%, and 19%, respectively. Somatic mutations were found in 18% (2 of 11) of the HNPCC CRCs and 13% (4 of 32) of the MSI+ sporadic tumors, but not in MSI- cancers (P = 0.015). All somatic mutations occurred in the two 6(A) coding mononucleotide tracts in PTEN, suggestive of the etiological role of the deficient MMR. Immunohistochemical analysis revealed 31% (14 of 45) of the HNPCC CRCs and 41% (9 of 22) of the MSI+ sporadic tumors with absent or depressed PTEN expression. Approximately 17% (4 of 23) of the MSI- CRCs had decreased PTEN expression, and no MSI- tumor had complete loss of PTEN expression. Among the five HNPCC or MSI+ sporadic CRCs carrying frameshift somatic mutations with immunohistochemistry data, three had lost all PTEN expression, one showed weak PTEN expression levels, and one had mixed tumor cell populations with weak and moderate expression levels. These results suggest that PTEN frameshift mutations in HNPCC and sporadic MSI+ tumors are a consequence of mismatch repair deficiency. Further, hemizygous deletions in MSI- CRCs lead to loss or reduction of PTEN protein levels and contribute to tumor progression. Finally, our data also suggest that epigenetic inactivation of PTEN, including differential subcellular compartmentalization, occurs in CRCs.
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PMID:PTEN mutational spectra, expression levels, and subcellular localization in microsatellite stable and unstable colorectal cancers. 1216 69

The erbB2 receptor tyrosine kinase and the CD44 transmembrane glycoprotein interact with one another in numerous cell types. This interaction helps to maintain erbB2 activity that contributes to tumor progression. We investigated whether CD44 and erbB2 similarly interact in endometrial carcinomas in vitro and in situ. In contrast to other carcinomas, CD44 did not colocalize with erbB2 in any of the 51 cases of endometrial cancer analyzed. CD44 also did not coimmunoprecipitate or colocalize with erbB2 in two endometrial carcinoma cell lines. We propose that the lack of CD44-erbB2 interactions may reduce the contribution of erbB2 to endometrial carcinoma progression.
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PMID:Endometrial carcinoma cells are nonpermissive for CD44-erbB2 interactions. 1237 51

Previously, we demonstrated that connexins (Cxs) showed aberrant localization and expression in most endometrial hyperplasia and carcinoma samples, indicating that during endometrial carcinogenesis, loss of gap junctional intercellular communication (GJIC) may occur at relatively early stages. In the present study, we focused on the correlations between GJIC and the expression of the E-cadherin and its 5' CpG island methylation in endometrial cancer cells and tissues to investigate their roles in the carcinogenesis and tumor progression of endometrial cancer. In this study, three of the 10 cell lines investigated, Ishikawa, RL-952 and KLE, in which both Cxs and E-cadherin mRNA were expressed, exhibited GJIC by scrape-loading/dye transfer. On the other hand, the other seven cell lines, in which either or both Cxs and E-cadherin mRNA were negative or weakly expressed, did not show GJIC. HEC-50, HEC-1B and HEC-108, in which Cxs were positively expressed but E-cadherin was negatively expressed, showed cytoplasmic localization of Cxs by immunohistochemistry. All five lines, which showed the weak expression of E-cadherin, had E-cadherin 5' CpG island methylation. By immunohistochemistry of 56 endometrial carcinomas, 13 of 27 methylated samples showed weak expression of Cx26 and the other 14 showed diffuse localization in cytoplasm. On the other hand, of 29 unmethylated samples, two showed cell-cell localization, 25 weak expression and two diffuse localization. Furthermore, E-cadherin expression was revealed to be drastically down-regulated by E-cadherin antisense oligonucleotides that post-transcriptionally down-regulated E-cadherin expression and in the cell, the localization of Cxs were changed from the cell-cell borders to the cytoplasm, and GJIC also decreased. The results indicated that 5' CpG island methylation, which caused loss of E-cadherin expression, indirectly caused the suppression of GJIC by aberrant localization of Cxs in endometrial carcinoma cells.
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PMID:Suppression of gap junctional intercellular communication via 5' CpG island methylation in promoter region of E-cadherin gene in endometrial cancer cells. 1289 2

Human heparanase has been shown to function in tumor progression, metastatic spread, and tumor angiogenesis. The aim of the present study was to assess heparanase expression in endometrial cancer in correlation with neovascularization and clinicopathological factors. Forty endometrial cancers were obtained from previously untreated patients (median age 55.5, range 33-78 years). The expression of heparanase mRNA was evaluated using a semiquantitative reverse transcriptase-polymerase chain reaction. Tumor angiogenesis was assessed using microvessel counting. The Mann-Whitney U test, one-factor ANOVA test, and Spearman's test were used to determine the relationship between heparanase expression, microvessel density, and clinicopathological parameters. The expression of heparanase mRNA was detected in 20 of 40 (50%) endometrial cancers, and was significantly correlated with FIGO stage IIIc (p=0.0075), the presence of lymph-vascular space involvement (p=0.0041), lymph node metastasis (p=0.0049), and histological tumor grade (p=0.0030). Microvessel density was also associated with FIGO stage IIIc (p=0.027), the presence of lymph-vascular space involvement (p=0.001), lymph node metastasis (p=0.038), ovarian metastasis (p=0.030) and histological tumor grade (p=0.0030). Moreover, we found a strong positive correlation between heparanase expression and microvessel density (r2=0.475, p=0.0001). These results suggest that the expression of heparanase may influence different malignant behaviors in endometrial cancer.
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PMID:Heparanase expression and angiogenesis in endometrial cancer. 1290 90

Vascular endothelial growth factor (VEGF) that activates endothelial cell growth induces angiogenesis, which is indispensable to tumor igenesis and tumor progression. On the other hand, tumor suppressor gene p53 has been considered to regulate VEGF expression, but the detailed relationship between them remains unclear. In this study, we aimed to study VEGF expression in endometrial carcinoma cells and the effect of p53 gene transfection on VEGF expression using p53-mutated endometrial carcinoma cell line, HEC-50B. Immunoblotting for detecting VEGF protein, p53 protein and beta-actin was performed using 11 endometrial carcinoma cell lines. Levels of VEGF in the cultured media were measured by Enzyme immunoassay(EIA). Transfection of wild p53 gene was carried out by SuperFect method in HEC-50B cells, which had mutant p53 gene and did not express p53 protein. The results of immunoblotting were analyzed by NIH image and expressed as values. The results of EIA were expressed as the relative value. The VEGF value was 0.8 +/- 0.3 (n = 6) in p53-wild group, whereas in p53-mutant group it was 1.6 +/- 0.8 (n = 5). VEGF expression was correlated significantly with p53 status (P < 0.05). VEGF levels in p53 gene-transfected cells and the conditioned medium were decreased in 48 hours after p53 gene transfection. VEGF expression was down-regulated by p53 in endometrial carcinoma cells.
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PMID:VEGF expression and its reguration by p53 gene transfection in endometrial carcinoma cells. 1297 25

Smad4 is a member of the Smad proteins, which are needed for mediating signals of transforming growth factor beta from the cell surface to the nucleus. Smad4 is also a tumor suppressor gene for cancers of the pancreas, colon, and lung. The aim of this study was to investigate the expression and prognostic significance of this gene product in endometrial cancer. Immunohistochemical staining for Smad4 was performed on formalin-fixed, paraffin-embedded specimens of endometrial tumors with an anti-Smad4 monoclonal antibody (clone B8): 97 primary endometrial carcinomas, 20 cases of endometrial hyperplasia, and 26 cases of metastases from endometrial carcinoma. The immunoreactivity of each tumor was correlated with the clinical and histopathologic parameters of the patients. Diffusely positive expression of Smad4 protein was detected in all 20 cases of endometrial hyperplasia and in most of the primary and metastatic endometrial cancers. The frequency of positive expression decreased progressively with tumor grade. Clinically, however, it was not associated with tumor progression, nor did it predict patient outcome. Although loss of heterozygosity at chromosome 18q21 (the location of the Smad4 gene) is frequent in endometrial carcinomas, the authors show in this immunohistochemical study that inactivation of this gene occurs infrequently in this tumor.
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PMID:Loss of Smad4 protein expression occurs infrequently in endometrial carcinomas. 1450 14

Stimulation of the endometrium by estrogens without the differentiating effect of progestins is the primary etiological factor associated with the development of endometrial hyperplasia and adenocarcinoma. However, the correlation between sex steroids and gap junctional intercellular communication (GJIC), which is considered to play an important role in the control of cell growth and differentiation, is not well known in endometrial carcinoma. In this study, we focused on the influence of estrogen and its receptor in connexin (Cx) expression and GJIC in endometrial carcinoma cells, established stable clone IK-ER1 overexpressing ER-alpha to transfect the expression vector and analysed them in various hormonal conditions. The growth of IK-ER1 was accelerated by 17beta-estradiol and the acceleration of the 5-bromo-25-deoxyuridine labeling index was observed. GJIC was assayed by scoring the number of dye-coupled cells after microinjection of single cells with Lucifer-Yellow, and subcellular localization of Cx26 and Cx32 was analysed by immunocytochemistry. In the presence of estradiol, dye-coupled cells of IK-ER1 were significantly reduced compared to those without estradiol and the reduction was completely inhibited by adding ICI182.780, a pure antiestrogen substrate. Cxs were detected as only small spots by immunocytochemistry, and Western blotting showed that the expression was decreased. These results suggest that activation of ER-alpha by estrogen results in tumor progression by stimulating cell growth and suppressing GJIC via suppression of the expression of Cxs in endometrial carcinogenesis.
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PMID:Overexpression of estrogen receptor-alpha gene suppresses gap junctional intercellular communication in endometrial carcinoma cells. 1476 40

Vascular endothelial growth factor (VEGF) and such plasminogen activation system components as uPA, PAI-1 and tPA were determined by enzyme immunoassay methods in endometrial tumors from 121 patients and 18 samples of endometrial hyperplasia of varying degree. Endometrial carcinoma concentrations of uPA vs. PAI-1 were significantly higher than those in hyperplasia. Significant direct correlations--uPA vs. VEGF, uPA vs. PAI-1 and PAI-1 vs. VEGF--were established in endometrial tumors, and inverse ones for tPA vs. uPA and tPA vs. VEGF. A marked correlation with prognostic factors was found for PAI-1 and VEGF: levels of these proteins were relatively higher in cases of tumor progression (FIGO stage and deeper myometrial invasion), poor cell differentiation, and loss of hormone sensitivity. Higher uPA expression was associated with deeper myometrial invasion while, in endometrial tumors with unfavorable prognosis, it was VEGF level alone that was significantly higher.
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PMID:[Vascular endothelial growth factor and plasminogen activators in endometrial carcinoma and hyperplasia]. 1497 16


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