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首页> 外文学位 >Differential epigenetic signatures between normal uterine smooth muscle cells (SMC) and leiomyoma cells (LM) and their association with estrogen responses.
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Differential epigenetic signatures between normal uterine smooth muscle cells (SMC) and leiomyoma cells (LM) and their association with estrogen responses.

机译：正常子宫平滑肌细胞（SMC）和平滑肌瘤细胞（LM）之间的差异表观遗传学特征及其与雌激素反应的关系。

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摘要

Differential gene expression between uterine leiomyoma (fibroids) and adjacent normal smooth muscle has been found in clinical tissues and cell cultures. The purpose of this study is to investigate whether there are differential epigenetic signatures and their involvement in differential gene expression, apoptosis and estrogen responses between two uterine stable cell lines, uterine leiomyoma UtLM-hT (LM) and normal uterine smooth muscle cell lines UtSM-hT (SMC). We first analyzed DNA methylation status using a cancer methylation panel bead array and our data showed that there are differential methylation patterns between the two cell lines. We then selected nine genes with significant differential methylation patterns from the bead array and verified that eight of the nine selected genes show significant differential gene expression between the two cell lines. Additionally, four of the eight genes that demonstrate differential gene expression respond to treatment with a demethylation agent, 5-Aza-2'-deoxycytidine (DAC). Cellular retinol binding protein 1 (CRBP-1) and Tumor necrosis factor super family 10 (TNFSF10) are genes that shows significant differential methylation patterns, gene expression, and responses to DAC between LM and SMC. Altered extracellular matrix (ECM) genes and reduced apoptosis are found in LM and are associated with epigenetic silenced CRBP-1 and TNFSF10 genes. Hypersensitivity to estrogen was not changed with epigenetic modification in leiomyoma. However, differential Fos gene expression, before and after E2 treatment, between LM and SMC were both reduced after epigenetic modifications.;This is the first study to investigate systemically with a methylation bead array the possible role of epigenetic changes and their associated biological impacts and potential epigenetic therapy in uterine leiomyoma.
机译：在临床组织和细胞培养物中已发现子宫平滑肌瘤（肌瘤）与相邻正常平滑肌之间的差异基因表达。这项研究的目的是研究两种子宫稳定细胞系子宫平滑肌瘤UtLM-hT（LM）和正常子宫平滑肌细胞系UtSM-之间是否存在差异的表观遗传学特征及其是否参与差异基因表达，凋亡和雌激素反应。 hT（SMC）。我们首先使用癌症甲基化面板微珠阵列分析了DNA甲基化状态，我们的数据表明两种细胞系之间存在差异的甲基化模式。然后，我们从微珠阵列中选择了9个具有明显差异甲基化模式的基因，并验证了9个选定基因中的8个在两个细胞系之间显示了明显的差异基因表达。此外，显示差异基因表达的八个基因中的四个对脱甲基剂5-Aza-2'-脱氧胞苷（DAC）的处理产生响应。细胞视黄醇结合蛋白1（CRBP-1）和肿瘤坏死因子超家族10（TNFSF10）是具有显着差异的甲基化模式，基因表达以及LM和SMC之间对DAC的响应的基因。 LM中发现改变的细胞外基质（ECM）基因和减少的细胞凋亡，并与表观遗传沉默的CRBP-1和TNFSF10基因相关。在平滑肌瘤中，表观遗传修饰不会改变对雌激素的超敏反应。然而，表观遗传修饰后，LM和SMC之间在E2处理之前和之后的Fos基因差异表达均降低了;这是首次使用甲基化磁珠阵列系统研究表观遗传变化及其相关生物学影响的可能的研究。子宫平滑肌瘤的潜在表观遗传治疗。

著录项

  • 作者

    Chiang, Tung-chin.;

  • 作者单位

    Tulane University.;

  • 授予单位 Tulane University.;
  • 学科 Biology Molecular.;Womens Studies.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 125 p.
  • 总页数 125
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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