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)

In order to study ezrin function in tumor growth and invasion, we used two cell lines of human endometrial cancers. Ishikawa, the low-metastatic endometrial cancer cell line, and its subclone (mEIIL) with high-metastatic activity and higher ezrin expression were treated with a ezrin antisense phosphorothioate oligonucleotides (ePONs) pulse four times before the in vitro growth assay and Matrigel invasion assay. ePONs significantly suppressed the number of both cells that penetrated through Matrigel membrane (inhibition rate; 40.1 +/- 7.5% (Ishikawa), 42.7 +/- 2.4% (mEIIL), mean +/- SD, n = 6, P < 0.05, Student's t-test), whereas they showed no effect on cell proliferation. Ezrin expression at the protein level was inhibited by ePONs. These data suggest that ezrin expression is required for invasion. The association of high ezrin expression in mEIIL and its higher ability to migrate through Matrigel may at least in part indicate functional significance of ezrin in endometrial cancer metastasis.
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PMID:Ezrin, a membrane-cytoskeletal linking protein, is involved in the process of invasion of endometrial cancer cells. 1066 86

In this article our findings concerning estradiol-induced changes in steroid receptor activation, cell kinetics and tumor growth regulation during in vivo and in vitro progression of human endometrial adenocarcinomas are reviewed. We found major changes such as alterations in estrogen receptor function and post-receptor alterations in tumor growth regulation. Our results suggest that although the development of these alterations is genetically determined, they may to some extent be modified by circulating estradiol levels. No biological changes were found, suggesting that the use of menopausal estrogen replacement therapy by women with non-diagnosed endometrial cancer may increase their death rate.
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PMID:[The effect of estradiol on human endometrial cancer. Experimental in vivo and in vitro studies]. 1090 Aug 96

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

In the present study, we analyzed the expression of a multifunctional cytokine, interleukin-8 (IL-8), in metastatic endometrial carcinoma cells. Our data demonstrate that human serous papillary endometrial adenocarcinoma (SPEC) and human endometrial adenocarcinoma (HEC) cells expressed steady-state IL-8-specific mRNA transcript and secreted IL-8 protein. The levels of IL-8 mRNA in SPEC-2 cells established from stage IV serous papillary adenocarcinoma were three-fold higher as compared to endometrial adenocarcinoma cells, HEC-1 A, established from stage IA endometrial cancer. Further, we observed higher levels of IL-8 mRNA and protein expression in the metastatic variants of SPEC-2 and HEC-1A cells as compared to the parent cell lines, demonstrating that IL-8 expression was associated with metastatic potential. Further, the treatment of endometrial carcinoma cells with inflammatory cytokines, IL-1beta and tumor necrosis factor-alpha (TNF-alpha), demonstrated that IL-1beta and TNF-alpha induced IL-8 expression in endometrial cancer cells. IL-1beta was a more potent inducer of IL-8 expression than TNF-alpha in our studies. These data demonstrate that constitutive and induced IL-8 expression in endometrial carcinoma cells might be an important regulatory mechanism of tumor growth and metastasis.
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PMID:Expression of interleukin-8 in human metastatic endometrial carcinoma cells and its regulation by inflammatory cytokines. 1128 34

Tamoxifen (TAM) is a highly effective selective estrogen receptor (ER) modulator used extensively for the treatment and prevention of breast cancer. However, prolonged treatment of women with TAM may be a risk factor for endometrial cancer, and research in our laboratory is focused on the development of selective aryl hydrocarbon receptor modulators that can be used in combination with TAM to improve its efficacy in the breast and inhibit TAM-induced endometrial effects. This study investigated the effects of the selective aryl hydrocarbon receptor modulators 6-methyl-1,3,8-trichlorodibenzofuran (6-MCDF) alone and in combination with TAM in the carcinogen-induced mammary tumor model and in the ovariectomized uterotropic assay using female Sprague Dawley rats. The lowest effective dose of 6-MCDF that inhibited tumor growth was 50 microg/kg/day, and TAM was antitumorigenic at a dose of 100 microg/kg/day. In animals cotreated with TAM + 6-MCDF at doses of 100, 50, or 25 microg/kg/day of each compound, complete inhibition of mammary tumor growth was observed at all doses, and the results are consistent with a more than additive antitumorigenic response for the low dose group (25 + 25 microg/kg) and additive interactions at the 50 and 100 microg/kg doses. In a separate experiment, 6-MCDF (800 microg/kg) inhibited TAM-induced peroxidase activity and progesterone receptor binding in the ovariectomized rat uterus but did not affect TAM-induced bone growth in ovariectomized rats. This study also investigated the effects of TAM and 6-MCDF alone and in combination on ERalpha protein levels in MCF-7 human breast cancer cells as a model for studying interactions between these compounds. The results show that 6-MCDF decreased TAM-induced ERalpha levels in the absence or presence of 17beta-estradiol through proteasome activation, and these interactions may contribute to the observed combined antitumorigenic effects of these compounds.
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PMID:Tamoxifen-induced antitumorigenic/antiestrogenic action synergized by a selective aryl hydrocarbon receptor modulator. 1135 3

Tamoxifen, now in use in the breast cancer clinic worldwide, was a study subject of controversy showing an estrogenic property on one occasion and an anti-estrogenic property on another occasion. The outcomes of 4 case-control studies of tamoxifen use were disclosed through 4 publications in 1998. The contents of these reports were intriguing, not only to surgeons of breast cancer clinics, but also to researchers of oncological science in general. The results of 4 research groups, being compatible with each other, were summarized in succession as follows: a) long-term use of tamoxifen reduced the occurrence of estrogen receptor (ER)-positive tumors by 69%, but no difference in the occurrence of ER(-) tumors was seen; b) the incidence of endometrial cancer was increased in the tamoxifen group; c) in women who did not have breast cancer and who had had a hysterectomy, there was no difference of breast cancer occurrence between the placebo- and tamoxifen-arms. Nevertheless, there was a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial; d) there was also no case-control difference of breast cancer occurrence between tamoxifen- and placebo-groups, when tested in a healthy population with a strong family history; e) the beneficial effect of long term use of tamoxifen in patients with early breast cancer, as assessed in terms of recurrence reduction, survival improvement and suppression of a contralateral tumor growth, was restricted to ER(+) patients; f) there was a positive correlation between the duration of tamoxifen use and the occurrence of endometrial cancer. All these observations provide strong support to the concept of the steroid criminal theory of human carcinogenesis in general. On the basis of both tamoxifen data and other information surrounding the hormonal aspect of human carcinogenesis of multiple tumors including breast cancer, we propose that the steroid generating system, as linked to the ever changing environment, plays a cardinal role as the transmitter of steroidal signals that can be taken as a "go" sign by the local oncogene-tumor suppressor gene complex of one target tissue and as a "stop" sign by that of another target tissue. The fitness of the tamoxifen data to the steroid carcinogenesis concept was discussed in the light of experimental pathology of chemical carcinogens, including the mammocarcinogen 7,12-dimethyl-benz(a)anthracene.
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PMID:The nature of tamoxifen action in the control of female breast cancer. 1169 24

A herbal complex consisting of Hoelen, Angelicae radix, Scutellariae radix and Glycyrrhizae radix suppressed cell viability and telomerase activity in hormone-refractory and chemo-resistant cancer cell lines, namely poorly differentiated uterine endometrial cancer cell line AN3 CA, adriamycin-resistant breast cancer cell line MCF7/ADR and cisplatin-resistant ovarian cancer cell line A2780. Furthermore, the herbal complex suppressed the expression of the full length of human telomerase reverse transcriptase (hTERT), which is related to telomerase activity. This indicates that the herbal complex can suppress the tumor growth of chemoendocrine resistant cancers, at least in part via suppression of telomerase activity associated with down-regulated hTERT.
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PMID:Herbal complex suppresses telomerase activity in chemo-endocrine resistant cancer cell lines. 1176 37

Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing production of angiogenic factors. These mechanisms require clarification in endometrial cancer. COX-2 expression was examined by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR) in endometrial cancer, endometrial hyperplasia, and normal endometrium in various phases. We investigated the relationship between COX-2 expression and clinicopathologic variables, microvessel count, and expression of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). Immunohistochemistry demonstrated COX-2 protein in cancerous epithelial cells but not in stromal cells. COX-2 expression in epithelial cells was significantly greater in endometrial cancer (n = 63) and endometrial hyperplasia (n = 6) than in normal endometrium in any phase (n = 53). Although COX-2 did not correlate with any conventional clinicopathologic factor in patients with endometrial cancer, COX-2 expression was associated with high microvessel count, VEGF expression, and TP expression. By combined analysis of COX-2, VEGF, and TP, tumors with high expression of at least one factor had a significantly higher microvessel count than tumors expressing little of the three factors. We confirmed upregulation of COX-2 mRNA expression by RT-PCR in endometrial cancer (n = 17) compared to normal endometrium (n = 12). COX-2 mRNA expression significantly correlated with VEGF mRNA expression in these tumors. COX-2 is upregulated in endometrial cancer and facilitates tumor growth via angiogenesis produced in associated with VEGF and TP. Specific inhibition of COX-2 may be a useful therapeutic intervention in endometrial cancer.
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PMID:Cyclooxygenase-2 expression in endometrial cancer: correlation with microvessel count and expression of vascular endothelial growth factor and thymidine phosphorylase. 1195 47

The angiogenic peptide adrenomedullin (ADM) has been implicated as a mediator of the increased risk of endometrial hyperplasia and cancer resulting from the use of tamoxifen for the treatment and prevention of breast cancer. ADM has been shown to be induced by tamoxifen in the endometrium and to be a growth factor for endometrial endothelial cells in vitro. We have now shown ADM to be strongly angiogenic in the mouse subcutaneous sponge angiogenesis assay. To examine the role of ADM in tumor growth, the ADM cDNA was transfected into endometrial carcinoma cells followed by xenografting into athymic mice. Two endometrial cancer cell lines were employed, those in which transfection and expression of ADM resulted in no effect on growthin vitro (Ishikawa cells) and those in which expressionof exogenous ADM stimulated in vitro growth (RL95.2 cells). A clear enhancement of tumor growth was seen with both cell lines but the effect was far greater with the RL95.2 cells. We conclude that ADM is pro-tumorigenic by stimulating either angiogenesis alone or by stimulating angiogenesis and carcinoma cell growth directly. The combined activities lead to a striking increase in tumor growth. These results provide the first direct evidence of tumorigenic activity of ADM and provide further support for ADMs involvement in tamoxifen induced endometrial neoplasia.
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PMID:Adrenomedullin promotes formation of xenografted endometrial tumors by stimulation of autocrine growth and angiogenesis. 1197 40

Survivin is a new member of the inhibitor of apoptosis family of anti-apoptotic proteins. It has been reported that survivin is expressed during fetal development and in cancer tissues. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression of survivin in human endometrial carcinomas. We analyzed serial frozen sections for survivin protein expression in 31 cases of endometrial carcinoma and 20 cases of normal endometria by fluorescent immunohistochemistry. We analyzed the relationship between the percentages of survivin-stained cells and the patient's characteristics, including clinical stage, histological grade, presence of invasion to >1/2 myometrium, clinical outcome, and survival rate. Survivin was weakly detected in some normal endometria in the proliferative phase (0-5.1%) and in the secretory phase (0-15.8%). There was, however, abundant survivin immunoreactivity in the nucleus and/or cytoplasm of the endometrial carcinoma cells. Scoring on the basis of the percentage of positive cells indicated that survivin expression was significantly associated with proliferating cell nuclear antigen-labeling index, clinical stage, histological grade, the presence of invasion to >1/2 myometrium, clinical outcome, and survival rate (P<0.01, respectively). We conclude that the survivin protein is a defining diagnostic marker for endometrial carcinomas that may also yield prognostic information.
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PMID:Survivin expression correlates with clinical stage, histological grade, invasive behavior and survival rate in endometrial carcinoma. 2400 29


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