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 medical clinics or experiments, progesterone (P) has been used for treatment of adenomatous hyperplasia or cancer of the endometrium. In the present paper, effects of P in combination with or without estradiol-17 beta (E2) on the estrogen receptor (ER) and thymidine kinase (TK) activity in immature rat uterus are described. P has been reported to interfere with the replenishment of the cytoplasmic ER of the rat uterus. In the present study, no translocation of the cytoplasmic ER to the nucleus was found after the injection of P, whereas P slightly enhanced the wet weight and the TK activity of the uterus. The TK activity increased 20 to 30 times the control level at 30 hours after the injection of E2. However, the enzyme activity induced by E2 was inhibited by P which was approximately 1,000-fold or more dose of E2. This enzyme was separated into isozymes by DEAE-cellulose column chromatography. Induction of the specific TK isozyme, which was induced by E2 in immature rat uterus and closely related to DNA synthesis, was found to be inhibited by P.
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PMID:[Estrogen and progesterone interactions on the estrogen receptor and thymidine kinase in the immature rat uterus]. 715 94

The involvement of altered c-jun activity in medroxyprogesterone acetate (MPA)-induced growth responses in human endometrial carcinoma cells is examined in this paper. Under conditions of MPA-induced growth inhibition, c-jun mRNA and protein levels are decreased in Ishikawa cells. This decrease is accompanied by an overall decrease in endogenous AP-1 activity in these cells. Only a transient decrease in c-jun mRNA level without any effect on endogenous AP-1 activity is seen in HEC-50 human endometrial carcinoma cells after MPA treatment. Increased expression and activity of c-jun was achieved in Ishikawa cells by transient transfection of Rous sarcoma virus (RSV)-c-jun alone or RSV-c-jun plus AP-1 binding sites (5x-4-beta-phorobol 12-myristate 13-acetate response element-thymidine kinase-chloramphenicol acetyltransferase), respectively. These treatments were accompanied by an increase in cell numbers due to MPA treatment in Ishikawa cells. In contrast, MPA treatment of mock-transfected, RSV-jun-B-transfected, or 5x-4 beta-phorbol 12-myristate 13-acetate response element-thymidine kinase-chloramphenicol acetyltransferase alone transfected Ishikawa cells resulted in the expected decrease in cell numbers. The data presented in this paper are consistent with the hypothesis that altered c-jun activity in a target cell can alter proliferative responsiveness to MPA and suggest that such a mechanism may be associated with resistance to hormonal manipulative therapies used in the treatment of both human breast and endometrial cancer.
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PMID:Enhanced c-jun activity alters responsiveness to medroxyprogesterone acetate in Ishikawa human endometrial carcinoma cells. 814 69

The mouse lactoferrin gene responded to forskolin, 12-O-tetradecanoyl phorbol-13-acetate, and epidermal growth factor (EGF) stimulation via two adjacent enhancer elements, the cAMP response element (CRE) and EGF response element (EGFRE), collectively referred to as the mitogen response unit. In this report, we examined the minimal promoter and enhancer elements of the mouse lactoferrin gene that are required for EGF-induced transcriptional activation. We found that the CRE and noncanonical TATA box (ATAAA) are the minimal promoter elements for basal activity of the chloramphenicol acetyltransferase (CAT) reporter construct whereas the EGFRE is needed for an additional activity induced by EGF in transiently transfected human endometrial carcinoma RL95-2 cells (RL95-2). The EGFRE, however, did not function in heterologous promoters [SV 40 and thymidine kinase (TK)]. Therefore, EGF-stimulated lactoferrin gene activity is promoter specific in RL95-2 cells. In transiently transfected cells, EGF and forskolin showed synergistic effects on the CAT reporter that contained both response elements. Mutation made at either element or insertion of extra nucleotides between the two elements severely affected EGF-stimulated activity. Nuclear protein prepared from RL95-2 cells formed three complexes (A, B, and C) with the oligonucleotides containing both EGFRE and CRE in electrophoretic mobility shift assay. A new complex (E) was detected with the nuclear protein of EGF-treated cells. By oligonucleotide competition experiments, we demonstrated that the complex E was generated by protein bound to CRE. EGF-induced binding activity could be abolished by calf intestinal alkaline phosphatase but not by the protein synthesis inhibitor, cycloheximide. Therefore, binding of a preexisting phosphoprotein to the CRE region could be one of the requirements for EGF-induced mouse lactoferrin gene promoter activity.
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PMID:Promoter-specific activation of mouse lactoferrin gene by epidermal growth factor involves two adjacent regulatory elements. 877 33

To investigate the functional differences between estrogen receptor (ER) alpha and beta subtypes, we studied the expression and the transcription stimulating activities of these receptors. RT-PCR has demonstrated that ER alpha is expressed at a high level in MCF-7 cells derived from human breast cancer. Both ER alpha and ER beta were expressed at a lower level in HOS-TE85 and Saos2 cells derived from human osteosarcoma. Chloramphenicol acetyltransferase reporter assay detected the transcriptional activation by the endogenous receptor only in MCF-7 cells. Agonistic effect of tamoxifen was observed as strong as that of 17beta-estradiol on ERE activation in MCF-7 cells at the concentration of 10(-7) M when ERE-containing reporter is constructed with beta-globin promoter. The effect of tamoxifen was not apparent when the reporter was constructed with thymidine kinase promoter, suggesting that the differential gene activation between tamoxifen and estrogen may take place depending upon ERE-promoter context. Agonistic activity of tamoxifen was also detected in COS-7 and Saos-2 cells, but not in HEC-1 cells derived from human endometrial carcinoma via exogenously expressed ER. Interestingly, this effect was ER alpha specific. Thus, we demonstrate that agonistic effect of tamoxifen depends on the cell type, ERE-promoter context, and ER subtype. These parameters would explain at least a part of the tissue specific effects of antiestrogens in vivo.
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PMID:Agonistic effect of tamoxifen is dependent on cell type, ERE-promoter context, and estrogen receptor subtype: functional difference between estrogen receptors alpha and beta. 922 41

We investigated whether retrovirus-mediated transfer of the herpes simplex thymidine kinase gene into a human endometrial carcinoma (EC4) cell line can sensitize these cells to the prodrug ganciclovir (GCV) and thereby provide a therapeutic option for this cancer. A retrovirus encoding for the herpes simplex virus tip-1 (HSV) thymidine kinase (tk) gene was generated in which expression of tk is under control of the myeloproliferative sarcoma virus (MPSV) promoter/enhancer. We used human mutated dihydrofolate reductase (DHFR) cDNA as a selectable marker. Expression of tk was confirmed by Northern blot analysis and reverse transcription polymerase chain reaction. We demonstrated that the combination of retrovirally mediated tk gene transfer and GCV treatment effectively inhibits proliferation and causes death of EC4 cells in vitro. A bystander killing effect was observed when 90% of uninfected tumor cells were mixed with only 10% of HSVtk-infected cells. We suggest that a gene therapy approach to endometrial carcinoma can be established using retroviral transfer of HSVtk to tumor cells and subsequent administration of GCV.
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PMID:Gene therapy for endometrial carcinoma with the herpes simplex thymidine kinase gene. 1068 1

Advanced peritoneal carcinomatoses is very difficult to treat. We have explored the potential therapeutic application of gene therapy using cationic liposomes in this disease. The lacZ gene was introduced in vitro into ovarian and endometrial cancer cells using cationic liposomes. The transfection efficiency was similar to that of commercially available liposomes in serum-free medium (11.0-20.9% vs. 5.4-26.0%). In serum-containing medium, the efficiency was 1.9-18.1%, which is comparable with the efficiency in serum-free medium. However, the efficiency of commercial liposomes decreased drastically to between 0.1% and 4.7% in the serum-containing medium. When cultured cells were transfected with the herpes simplex virus thymidine kinase (HSV-tk) gene and ganciclovir (GCV) was added, the anti-tumor effect of GCV was 47-640 times greater than when the same experiment was performed with lacZ gene. Evaluation of anti-tumor effect was performed with the MTT assay. In vivo, the HRA and mEIIL ascitic mice were treated with HSV-tk gene and GCV using the peritoneal route, a significant prolongation of the mean survival time was observed by Kaplan-Meier analysis (16-18 days and 15-30 days, respectively, p < 0.05). These results indicate a potential role for gene therapy in the treatment of advanced intraperitoneal carcinomatoses using the novel cationic liposomes.
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PMID:In vitro and in vivo evaluation of novel cationic liposomes utilized for cancer gene therapy. 1679 60