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)

Fas ligand induces cell death by means of apoptosis in a variety of cell types when cross-linked with its natural receptor, Fas. GnRH receptor-bearing tumors undergo apoptosis in vivo and in vitro with GnRH agonists. To provide a potential association of the Fas system with the antiproliferative signaling process of GnRH receptor, we have evaluated the regulation of Fas ligand expression in GnRH receptor-positive tumors and cloned cell lines known to have substantial GnRH receptors. Surgically removed uterine endometrial carcinomas and ovarian carcinomas had been screened for GnRH receptor expression before analysis. Fas ligand protein was characterized by immunoblotting of membrane proteins with the specific antibody. Fas ligand messenger RNA was determined by RT-PCR using oligonucleotide primers synthesized according to the published Fas ligand sequence. Incubation with a GnRH analog (1 mumol/L) induced the expression of Fas ligand messenger RNA and immuno-reactive Fas ligand with a lag time of 48 h in cloned cell lines (endometrial carcinoma HHUA cells, and ovarian carcinoma SK-OV-3 and Caov-3 cells). There was no detectable Fas ligand expression within 24 h. The stimulatory effect of GnRH on Fas ligand protein expression revealed a dose dependency; a half-maximal effect occurred with 10 nmol/L GnRH analog (P < 0.01). The stimulated Fas ligand expression could be neutralized by displacement of GnRH from its receptor by GnRH antagonist antide. Cells isolated from GnRH receptor-bearing ovarian carcinomas and uterine endometrial carcinomas gave identical results to those obtained in cloned cell lines. These data demonstrate the functional coupling of stimulated Fas ligand expression to GnRH receptor activation. Increased Fas ligand level within the GnRH receptor-bearing tumors might promote apoptotic cell death through attack on intratumoral Fas-positive cells that could, at least in part, account for the antiproliferative action of the hormone.
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PMID:Evidence for tight coupling of gonadotropin-releasing hormone receptor to stimulated Fas ligand expression in reproductive tract tumors: possible mechanism for hormonal control of apoptotic cell death. 946 52

Gonadotropin-releasing hormone (GnRH) receptor-bearing tumors undergo apoptosis in vivo and in vitro with GnRH analogs. We recently showed that GnRH stimulation induces intratumoral expression of the apoptosis-inducing Fas ligand in human reproductive tract tumors. To provide a potential association of Fas/Fas ligand system with the antiproliferative signaling process of GnRH receptor, we evaluated a correlation between the Fas ligand expression and the number of viable cells in two types of GnRH receptor-bearing endometrial carcinomas that differ in Fas content. Surgically removed uterine endometrial carcinomas had been screened for the presence of GnRH receptor and Fas before analyses. Fas ligand protein was characterized by immunoblotting of membrane proteins with the specific antibody. After a lag time of 2 days, incubation with a GnRH analog leuprolide (10 microM) induced significant growth inhibition of the Fas- and GnRH receptor-bearing cells (p<0.01). Time course analysis showed that Fas ligand production, which was already observed at day 2 (p<0.01), precedes the onset of reduction in viable cell number. The stimulatory effect of GnRH on Fas ligand expression and reduction of viable cells revealed dose-dependency. The analog at concentration of 10 microM induced up to 90% reduction in cell number. In contrast, the growth of Fas-negative cells was not affected by the analog, although Fas ligand appeared in response to the GnRH analog (p<0.01). These data demonstrate that the co-presence of Fas could be essential for GnRH to promote antiproliferative action in endometrial cancer cells carrying GnRH receptor. The hormone may act through intratumor Fas and Fas ligand system to induced growth inhibition in GnRH-sensitive tumors.
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PMID:Fas and Fas ligand system may mediate antiproliferative activity of gonadotropin-releasing hormone receptor in endometrial cancer cells. 962 9

The Fas-Fas ligand system is important in apoptosis mediated by CTLs and natural killer cells. The suppression of apoptosis contributes to carcinogenesis, as well as to a resistance to chemotherapy and radiotherapy. Circulating soluble Fas (sFas), which is generated by alternative mRNA splicing, can antagonize cell-surface Fas function. We investigated sFas levels in 64 patients with gynecological malignancies (28 cervical carcinomas, 18 endometrial carcinomas, and 18 ovarian carcinomas) and in 24 healthy female donors by using a Fas-specific ELISA. In each carcinoma group, serum sFas demonstrated a statistically significant elevation relative to levels in normal controls (P < 0.0001). Levels of serum sFas in patients with advanced cancer (FIGO stages III and IV) significantly exceeded those in patients with localized cancer (FIGO stages I and II) or those in normal control subjects (P < 0.0001). We divided the patients into two groups based on the level of serum sFas and examined the relationship between serum sFas levels and survival. No deaths occurred in the groups with cervical and endometrial cancer with a serum sFas level < 1.5 ng/ml. Survival rates in groups with cervical carcinoma, endometrial carcinoma, and ovarian carcinoma with a serum sFas level < 1.5 ng/ml exceeded those in groups with sFas levels of 21.5 ng/ml (P < 0.001, P = 0.128, and P = 0.012, respectively). Proportional hazard models demonstrated that serum sFas level was a statistically significant factor (P = 0.0196) for survival, as well as histological grade (P = 0.0168) in ovarian carcinoma.
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PMID:Serum soluble fas level as a prognostic factor in patients with gynecological malignancies. 1099 47

The process of apoptosis is responsible for normal cellular turnover in numerous tissues throughout the body. The endometrial layer of the uterus shows steroid-dependent cyclic changes in structure and function. After a proliferative and secretory phase, steroid support is withdrawn and the uterine epithelium is shed. We hypothesize that the apoptosis observed in endometrial cells following hormonal withdrawal is mediated by the Fas/Fas ligand (FasL) system. Normal endometrial cells and endometrial cancer cells were cultured in the presence of estrogen and progesterone. In order to mimic physiological hormonal changes, estrogen and progesterone were removed from the media. Apoptosis was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-dephenyl tetrazolium bromide (MTT) assay and propidium iodide staining, while Fas and FasL expression were evaluated by Western blot analysis. The endometrial cells expressed Fas and low levels of FasL. Withdrawal of estrogen and/or progesterone from the culture induced apoptosis causing an approximately 50% decrease in cell viability. This coincided with increased Fas and FasL expression. Treatment of the cells with anti-FasL antibody prevented cell death following hormonal withdrawal. Estrogen and progesterone therefore represent survival factors which hamper cell death by impeding the expression of apoptotic factors. Our results indicate that Fas-mediated apoptosis is important for endometrial cycling and suggest that dysregulation of the Fas/FasL interactions may have an important role in the development of endometrial cancer.
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PMID:Hormonal regulation of apoptosis and the Fas and Fas ligand system in human endometrial cells. 1199 42

Cytochrome c (CytC) released from mitochondria induces apoptosis in both normal and tumor cells. Expression of Fas ligand (FasL) helps maintain tumor cell survival by inducing apoptosis of Fas-bearing anti-tumor immune cells. A risk of endometrial cancer has been reported to associate with phytoestrogen consumption. Therefore the effects of phytoestrogens, genistein and daidzein, on FasL and CytC protein expression were examined in primary cultured porcine endometrial cells (PE) and human cancerous endometrial cells (RL95-2) by Western blot analysis. Both cells were cultured in standard medium (SM) and switched to estrogen-deprived medium (SF) with or without 17beta-estradiol (E, 1 nM), genistein (10 microM) or daidzein (10 microM) for 48 h. FasL (25 kDa) which was found only in RL95-2 cells was upregulated in SF compared to SM. Treatment of RL95-2 cells with E, daidzein or genistein significantly increased the FasL expression by 7-10 folds. In the present study, low level of CytC was detected in both cells cultured in SM but markedly increased in SF by 1.5-2 folds. The SF-induced increase in CytC level was reversed by genistein or daidzein while E suppressed CytC in PE cells, but not in RL95-2 cells. The findings suggest that genistein and daidzein appear to act as a survival factor by inhibiting intracellular apoptogenic initiator in both normal and cancer endometrial cells. In addition, estrogen and phytoestrogens inducing the death signal FasL expressed by cancerous endometrial cells may cause the tumor progression. Thus, consuming phytoestrogen as a supplement should be awareness in patient with endometrial cancer.
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PMID:Modulatory effects of phytoestrogens on the expression of Fas ligand and the release of cytochrome C in normal and cancerous endometrial cells. 2351 74