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)

A novel steroid and xenobiotic receptor (SXR) may be involved in chemoresistance, and we studied this receptor in endometrial cancer cell lines. The cisplatin (CDDP)-sensitive Ishikawa cell line and its CDDP-resistant sub-clone (ISIW+) were used. ISIW+ cells showed a much higher SXR expression. When Ishikawa cells were cultured with SXR anti-sense oligonucleotides (AS), the cells failed to pass crisis and did not gain cisplatin resistance. In an experiment using SCID mice, all AS-treated animals survived, whereas controls had 50% survival at 35 days. The present data indicate that SXR is a key system to induce, maintain and reverse a cisplatin-resistant phenotype in endometrial cancer cells.
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PMID:Steroid and xenobiotic receptor (SXR) is a key system for the acquisition of cisplatin resistance in endometrial cancer cells. 1276 Mar 8

Estrogen has been shown to contribute greatly to growth and development in endometrial cancer. And recent research has suggested that intratumoral production of estrogen may play important roles in this cancer tissue. On the other hand, pregnane X receptor (PXR), a new member of nuclear receptors, has been shown to mediate the genomic effects of steroid hormones, including estrogen and xenobiotics. And this receptor is thought to regulate the expression of the cytochrome P-450 3A (CYP3A) gene family, which plays important roles in the metabolism of endogenous steroids and xenobiotics. Various levels of PXR expression were found in endometrial cancer tissues but not normal tissues. Tissues showing high PXR expression showed significantly high expression of CYP3A4/7 and low expression of estrogen receptor (ER) compared with levels in tissues showing low PXR expression. In endometrial cancer cell lines, HEC-1 cells, which express high PXR and low ER and progesterone receptor, show a stronger transcriptional response of the PXR-CYP3A pathway to the PXR ligands, especially endocrine-disrupting chemical, than do Ishikawa cells. These data suggest that the steroid/xenobiotics metabolism in the tumor tissue through PXR-CYP3A pathway might play an important role, especially in alternative pathway for gonadal hormone and endocrine-disrupting chemical effects on endometrial cancer expressing low ER alpha.
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PMID:Expression and potential roles of pregnane X receptor in endometrial cancer. 1297 Mar 23

Recent studies have revealed that pregnane X receptor (PXR) can function as a master regulator to control the expression of phase I and phase II drug-metabolizing enzymes, as well as members of the drug transporter family, including multiple drug resistance (MDR) 1, which has a major role in multidrug resistance. Previously, we have demonstrated that steroid/xenobiotics metabolism by tumor tissue through the PXR-cytochrome P-450 3A (CYP3A) pathway might play an important role in endometrial cancer. In this study, we examined which endocrine-disrupting chemicals (EDCs) and anticancer agents might be ligands for PXR and whether these chemicals enhanced PXR-mediated transcription through two different PXR-responsive elements (PXREs), CYP3A4 and MDR1, in endometrial cancer cell lines. Some steroids/EDCs strongly activated PXR-mediated transcription through the CYP3A4-responsive element compared with the MDR1-responsive element, whereas these steroids/EDCs also enhanced the CYP3A4 expression compared with the MDR1 expression. In contrast, the anticancer agents, cisplatin and paclitaxel, strongly activated PXR-mediated transcription through the MDR1-responsive element compared with the CYP3A4-responsive element, whereas these drugs also enhanced the MDR1 expression compared with the CYP3A4 expression. We also analyzed how these ligands regulated PXR-mediated transcription through two different PXREs. In the presence of PXR ligands, there was no difference in the DNA binding affinity of the PXR/retinoid X receptor heterodimer to each PXRE, but there were different interactions of the coactivator to each PXR/PXRE complex. These data suggested that PXR ligands enhanced PXR-mediated transcription in a ligand- and promoter-dependent fashion, which in turn differentially regulated the expression of individual PXR targets, especially CYP3A4 and MDR1.
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PMID:The pregnane X receptor regulates gene expression in a ligand- and promoter-selective fashion. 1565 19

Recent studies have revealed that pregnane X receptor (PXR) can function as a master regulator to control the expression of drug-metabolizing enzymes, cytochrome P450 3A (CYP3A) family, and members of the drug transporter family, including multiple drug resistance 1 (MDR1). We demonstrated previously that steroid/xenobiotic metabolism by tumor tissue through the PXR-CYP3A pathway might play an important role in endometrial cancer and that PXR ligands enhance PXR-mediated transcription in a ligand- and promoter-dependent fashion, leading to differential regulation of individual PXR targets, especially CYP3A4 and MDR1. In this study, we investigated the potential contribution of PXR down-regulation by RNA interference toward the augmentation of drug sensitivity and the overcoming of drug resistance. We observed the protein levels of both CYP3A4 and MDR1 in PXR small interfering RNA (siRNA)-transfected cells were not increased in the presence of PXR ligands, paclitaxel, cisplatin, estradiol, or medroxyprogesterone acetate (MPA) compared with control siRNA-transfected cells. There was no PXR-mediated transactivation or augmentation of transcription by coactivators in the presence of these ligands. We then found that PXR down-regulation caused a significant increase in cell growth inhibition and enhancement of apoptosis in the presence of the anticancer agents, paclitaxel, cisplatin, and MPA. Finally, we demonstrated that PXR overexpression caused a significant decrease in cell growth inhibition and inhibited apoptosis in the presence of paclitaxel or cisplatin. These data suggest that PXR down-regulation could be a novel therapeutic approach for the augmentation of sensitivity to anticancer agents, or to overcome resistance to them, in the treatment of endometrial cancer.
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PMID:Down-regulation of pregnane X receptor contributes to cell growth inhibition and apoptosis by anticancer agents in endometrial cancer cells. 1763 47