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

Vascular endothelial growth factor (VEGF) is a previously discovered angiogenic factor that seems to influence the neoangiogenesis of neoplastic and non-neoplastic tissues. Substantial experimental evidence links tumor growth and metastasis with blood vessel formation. Tumor angiogenesis can be induced by factors released by the tumor cells themselves. A variety of transformed cell lines expresses the VEGF transcript and secretes an EGF-like protein, suggesting that this angiogenic factor may be one of the mediators of tumor angiogenesis. By Northern blot analysis and in situ hybridization, we investigated the expression of VEGF transcript in human ovarian and endometrial neoplasms. Messenger RNA encoding VEGF was detected in all tissues studied and was more densely expressed in endometrial carcinoma. VEGF expression was also identified in cells obtained from ovarian and endometrial ascitic fluid. VEGF mRNA, detected by in situ hybridization, was identified in the epithelial cells of endometrial adenocarcinoma. This distribution was localized primarily in the apices of the papillae. The prominence of VEGF mRNA levels in human ovarian and endometrial tumors demonstrates that VEGF may be involved in promoting tumor angiogenesis and stroma generation, acting as an endothelial cell mitogen.
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PMID:Vascular endothelial growth factor messenger ribonucleic acid expression in human ovarian and endometrial cancer. 903 63

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor associated with the degree of vascularity, progression, and metastasis of breast cancer, and cases of this disease with increased vascular density have a poor prognosis. We show that in T47-D human breast cancer cells, progesterone induces a dose-dependent increase of 3-4-fold in media VEGF levels, with a maximum response occurring at a concentration of 10 nM. This effect is blocked by the antiprogestin RU 486. In addition to progesterone, a number of synthetic progestins used in oral contraceptives (e.g., norethindrone, norgestrel, and norethynodrel), hormone replacement therapy (medroxyprogesterone acetate), and high-dose progestin treatment of breast cancer (megestrol acetate) also increase VEGF in the media of cultured T47-D cells. This effect is hormone specific and is not produced by estrogens, androgens, or glucocorticoids. Collectively, these observations suggest that the increase in VEGF caused by progestins is mediated by progesterone receptors present in T47-D cells. The induction of VEGF by progestins is also cell type specific and does not occur in human breast cancer cell lines MCF-7, ZR-75, or MDA-MB-231, nor in Ishikawa cells derived from a human endometrial carcinoma. This is the first report that progestins regulate VEGF expression in human breast cancer cells and raises the possibility that increased angiogenesis in response to endogenous progesterone or its therapeutically used analogues may play a role in cell growth or metastasis in a subset of human breast tumors.
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PMID:Progestin regulation of vascular endothelial growth factor in human breast cancer cells. 945 78

Vascular endothelial growth factor (VEGF) contributes to the early advancement of uterine endometrial cancers that conserve hormone dependency via angiogenic activity. This process prompted us to study sex steroidal suppression of VEGF expression in Ishikawa cells (a line of well-differentiated uterine endometrial cancer cells). Estrogen transiently induced VEGF subtype (VEGF165 and VEGF121) secretion from Ishikawa cells. Progestins (progesterone, medroxyprogesterone acetate (MPA) and 17 alpha-hydroxyprogesterone) suppressed the estrogen-induced events. In conclusion, progestins could suppress VEGF-related angiogenic potential, which contributes to tumor growth in the early stage of uterine endometrial cancers that conserve estrogen dependency.
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PMID:Progestins suppress estrogen-induced expression of vascular endothelial growth factor (VEGF) subtypes in uterine endometrial cancer cells. 1045 44

Angiogenesis is crucial for tumor growth and dissemination. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that promotes vascular growth and therefore tumoral growth and metastasis. Overweight, frequently associated with hyperinsulinemia, constitutes the major risk factor for endometrial carcinoma. Thus, elevated insulin levels may partly explain the increased risk of endometrial cancer observed in obese postmenopausal women. The aim of the present work was to test the role of insulin in the control of VEGF expression in endometrial carcinoma cells (HEC-1A). We have shown that insulin induced a biphasic expression of VEGF messenger ribonucleic acid, with an early, but low, induction (4 h of stimulation) and a delayed, but high, induction (24 h). The delayed effect of insulin on VEGF expression involved transcriptional and posttranscriptional regulation, as evidenced by the increased rate of VEGF transcription and the prolonged half-life of VEGF messenger ribonucleic acid. Simultaneously we observed higher levels of VEGF protein in the conditioned medium of stimulated cells compared with unstimulated ones. Therefore, insulin could contribute to the increased risk of endometrial carcinoma due to its ability to induce VEGF expression and thus participate in the maintenance of an angiogenic phenotype.
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PMID:Insulin up-regulates vascular endothelial growth factor and stabilizes its messengers in endometrial adenocarcinoma cells. 1123 25

Angiogenesis is critical for the growth and metastasis of endometrial cancer and is therefore an important therapeutic target. Vascular endothelial growth factor-A (VEGF-A) is a key molecule in angiogenesis, but the identification of related molecules and the angiopoietins suggests a more complex picture. We investigated the presence of transcripts for VEGF-A, VEGF-B, VEGF-C, VEGF-D, Angiopoietin-1 and Angiopoietin-2 in benign endometrium, atypical complex hyperplasia (ACH) and endometrioid endometrial carcinoma using in situ hybridisation. We confirmed the presence of VEGF-A mRNA in the epithelial cells of cancers examined (13 out of 13), but not in benign endometrium or ACH. We also demonstrate, using quantitative polymerase chain reaction, that levels of VEGF-B mRNA are significantly lower in endometrial cancer than benign endometrium. We conclude that loss of VEGF-B may contribute to the development of endometrial carcinoma by modulating availability of receptors for VEGF-A.
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PMID:Expression of the VEGF and angiopoietin genes in endometrial atypical hyperplasia and endometrial cancer. 1294 23

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

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

Vascular endothelial growth factor (VEGF) is associated with increased angiogenesis and aggressive tumour growth. We investigated the expression and clinical significance of VEGF and its receptors, flt-1 and KDR/flk-1, in patients with uterine endometrial carcinoma. The series consisted of 115 endometrioid endometrial adenocarcinoma patients with FIGO stage I-IV. Additionally, samples from 3 patients with adenoacanthoma and 12 patients with poor prognostic variants of endometrial carcinoma were examined. Immunohistochemical assessment was classified as negative or positive based on staining intensity. The median follow-up time of patients with endometrioid endometrial adenocarcinoma was 87 months. In endometrioid endometrial carcinomas, the positive immunostaining rate was 39% for VEGF, 65% for flt-1 and 68% for KDR/flk-1. There was a significant correlation between VEGF and both its receptors. Furthermore, this receptor expression was correlated between the two types of receptors. VEGF-, flt-1- and KDR/flk-1-positive immunostainings were not related to poor prognosis. We conclude that VEGF, flt-1 and KDR/flk-1 expressions are not useful prognostic markers for overall survival in patients with endometrioid endometrial carcinoma.
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PMID:VEGF and its receptors (flt-1 and KDR/flk-1) as prognostic indicators in endometrial carcinoma. 1586 79

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis in estrogen responsive tissues. Estrogen receptors alpha and beta regulate production of VEGF in both breast and endometrial cancer cells. Alternative splicing of ER-alpha mRNA generates a mixture of transcripts with various exon deletions in normal breast and breast cancer cells and some of these variants are overexpressed in breast cancer. We analyzed the role of exon-deleted variants of ER-alpha in regulation of VEGF production by simultaneous transient transfection of CHO and MDA-MB-231 cells with a VEGF promoter luciferase construct. Estrogen (10 nM) treatment resulted in a 6-fold increase in luciferase activity in cells transfected with the exon 3 deleted variant (ERDelta3) compared to a 2-fold activity induction in cells transfected with wild type ER-alpha. Exon 5 and exon 7 deleted variants were unable to induce activation of the VEGF promoter. Using specific deletion constructs of the VEGF promoter linked to luciferase, we showed that the majority of activation by ERDelta3 was restricted to the -70 to -88 bp fragment that contains two Sp1 sites. Site-directed mutagenesis of both Sp1 sites indicated that ERDelta3 activates the VEGF promoter through interaction with Sp1 proteins. ERDelta3, a variant frequently overexpressed in breast cancer, may significantly contribute to the production of VEGF thus resulting in enhanced tumor growth in vivo.
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PMID:Activation of vascular endothelial growth factor (VEGF) by the ER-alpha variant, ERDelta3. 1626 16

Vascular endothelial growth factor (VEGF) plays an essential role in normal uterine physiology and function as well as endometrial cancer and other uterine disorders. Recently we showed that estrogen regulation of VEGF expression in the rat uterus involves rapid recruitment of both estrogen receptor (ER)-alpha and hypoxia-inducible factor (HIF)-1alpha to the VEGF promoter. Estrogen is known to stimulate both the MAPK and phosphatidylinositol 3-kinase (PI3K) pathways, which have been linked to the activation of both of these transcription factors. Therefore, the involvement of these pathways in estrogen-induced VEGF expression was investigated. Inhibitors of the MAPK (U0126) or PI3K pathways (wortmannin or LY294002) were administered ip to immature female rats 1 h before 17beta-estradiol (E(2)) treatment. E(2) activation of both pathways occurred and was completely inhibited by the appropriate antagonist. Only PI3K inhibitors, however, blocked E(2) stimulation of VEGF mRNA expression and E(2)-induced uterine edema. In vivo chromatin immunoprecipitation analysis showed that this was associated with a failure of both HIF-1alpha and ERalpha to bind to the VEGF promoter. To determine whether inhibiting the PI3K pathway affected ERalpha induction of other estrogen target genes, the expression of creatine kinase B and progesterone receptor A/B was also examined. The expression of each was also inhibited by wortmannin, as was ERalpha binding to the creatine kinase B promoter. In conclusion, although estrogen activates both the MAPK and PI3K pathways in the rat uterus, activation of HIF-1alpha and ERalpha, and therefore regulation of VEGF gene expression is dependent only on the PI3K/Akt pathway. Furthermore, activation of the PI3K pathway appears to be a common requirement for the expression of estrogen-induced genes. These findings not only shed light on estrogen action in normal target tissues but also have important implications for cancer biology because excessive PI3K, HIF-1alpha, and VEGF activity are common in estrogen-dependent tumors.
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PMID:Estrogen-induced activation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor expression, and edema in the uterus are mediated by the phosphatidylinositol 3-kinase/Akt pathway. 1727 96


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