| Ovdrian cancer (OC) is the third frequently diagnosed malignant tUmors ofgynecology and the leading cause of cancer death in woman. Ovary not only couldsecrete some sex hormones, but also is a target organ for steroid hormones, such asestrogen, progesterone, androgen and glucocorticoids(GCs). In recent years, somestudies suggest, just like breast cancer and prostate cancef, steroid hormones mightplay an important role in the proliferation and differentiation of ovarian cancerAs steroid hormones, GCs exert profound effects on the proliferation anddifferentiation of many troes of normal and malignant cells, such as fibroblasts,lymphatic leukemia cells. However, up to noW there are few reports about the effectsof GCs on biological behaviors of ovdrian cancef, and some results are paradoxical.Therefore, it is necessary to haher explore the influence of GCs on ovarian cancer andthe underlying mechanisms.One major mechanism of GCs signaling in target cells is mediated byglucocorticoid receptor(GR), a member of the nuclear receptor suPerfamily whichincludes steroid hormone receptors, thyroid hormone receptors, retinoic acid receptof,etc.. Just like the other steroid receptors, once binding to its ligand, GR fOrmshomodimers, and interacts with the specific DNA sequence (glucocorticoid responseelement, GRE), and then regUlates the trapscriphon of target genes. In addition tointeraction with GRE, GC-GR also exeFts effects oftrallscriptional regulation on somegenes without GRE. For example,, some other laboratories and ours have recentlydemonstrated that DC-GR could suPPress the expression of p2l/WAFl, despite noGRE in its gene, by affecting other signal pathways or other transcriptional factors,such as TGF- 6 l and C/EBPa. The other possible mechanism is so-called"non-genomic mechanism", that is, GCs could exert their effects through interactionswith cell membrane instead of GR.The objective of this work is to investigate the effect of GCs on proliferation of ahuman ovarian cancer cell line(HO-89l0) that originated frOm high-metastasis ovarianserous cystadenocarcinoma, and the possible molecular mechanisms as well as toexplore of these effects. It was found that dexamethasone(Dex), an artificiallysynthetical GC, cou1d significant1y inhibit HO-89l0 cell proliferation in a dose- andtime- dependent ma-nner, and that this effect could be reversed by the GR amagonist,RU486, demonstrating that the inhibitory effect of Dex on the proliferation ofHO-89l0 is mediated by GR. Moreover, by flow cytometry(FCM) analysis, it wasshown that Dex could induce a recruitment of cells in the Go/GI phase with a reductionof cells in the S phase.The results stated above prompt us to identify the gene(s) involved in theDex-mediated growth inhibition of HO-89l0 ce1ls. Several lines of evidence suggestthat the p2l/WAFl gene might be one of the best candidates. As a cyclin-dependentkinase inhibitor(CDKI), p21/WAFl plays an important role in cell cycle arrest of cellsof different sources mainly by distUrbing the transition from Gof GI into S phase.Moreover. as mentioned above, it has been reported that GC-GR comp1ex cou1dregulate p2l/WAFl gene expression indirectly Keeping these in mind, we suspect thatGC might have potential effects on the p2l/WAFl expression in HO-89l0 cells. Forthis purpose, the expression of p21/WAF1 mRNA in HO-89l0 cells was analyzed byquantitative RT-PCR. It was fotmd that the p2l/WMl InRNA level in HO-89l0 cellswas increased significamly and raPidly by Dex in a dose- and time- dependent mannef,and this effect could be reversed completely by the GR antagonist, RU486, suggeshngp2l/Ml might be involved in Dex-mediated inhibition of HO-89l0 cellsproliferation.Considering p21/WAFl gene does not contaln GRE, we propose that there mightbe some other signal pathways, through which Dex induces p2l/WAF1 expressionindirectly. Reviewing the recent progress in relationships between stero...
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