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首页> 外文学位 >Expression of cohesin proteins and nano-architectural changes in rectal mucosa to assess risk of colon cancer based on field carcinogenesis.
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Expression of cohesin proteins and nano-architectural changes in rectal mucosa to assess risk of colon cancer based on field carcinogenesis.

机译：黏膜黏附蛋白的表达和直肠黏膜的纳米结构变化，以评估基于田间癌变的结肠癌风险。

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摘要

With 50,310 related deaths this year, colorectal cancer (CRC) has emerged as the second largest cause of cancer related deaths among Americans. While 70 million Americans are considered at-risk of developing CRC, it is highly curable if detected early. Cohesin proteins, which hold sister chromatids together during replication, have emerged as a potential biomarker in multiple cancer lines. Because of their probable role in DNA replication, DNA repair, chromatin nano-architecture, and gene expression, this paper assessed whether cohesion proteins could be used as a potential biomarker for colorectal cancer risk stratification. While cohesin protein mutations have been reported in different cancers and involved in chromosomal instability, its role in early cancer formation has yet to be observed. Using immunohistochemical and Quantitative Real Time PCR analysis, this thesis assessed the protein and RNA expression levels of cohesin proteins SA-1, NIPBL, and SMC3 from human biopsies at different stages and locations of colorectal cancer development. The results showed that SA-1, a structural cohesion subunit, was significantly (p<0.01) down regulated in cancerous compared to normal tissue. The SA-1 protein was also down regulated in the involved mucosa adjacent to CRC polyps. The cohesion loading protein, NIPBL, was also significantly (p<0.01) under expressed in cancerous versus normal tissue. The RNA expression analysis of rectal mucosa showed that SMC3 and SA-1 was over expressed two fold in patients harboring hyperplastic and adenomous polyps, giving evidence that cohesin proteins are differentially expressed throughout the field of carcinogenesis. Our results demonstrate for the first time that cohesion dysregulation is an early event in human colorectal cancer development and may serve as an important biomarker of field carcinogenesis.
机译：今年，大肠癌（CRC）死亡人数为50,310，是美国人中第二大死因。虽然有7000万美国人被认为患上CRC的风险很大，但如果能及早发现，这是可以治愈的。在复制过程中将姐妹染色单体结合在一起的粘着蛋白已成为多种癌症细胞中潜在的生物标志物。由于它们可能在DNA复制，DNA修复，染色质纳米结构和基因表达中发挥作用，因此本文评估了凝聚蛋白是否可以用作结直肠癌风险分层的潜在生物标记。虽然在不同的癌症中都报告了粘着蛋白蛋白突变，并涉及染色体不稳定，但尚未观察到其在早期癌症形成中的作用。本文采用免疫组织化学和实时定量PCR分析方法，评估了人类活检组织在结肠癌发展的不同阶段和位置的黏附蛋白SA-1，NIPBL和SMC3的蛋白质和RNA表达水平。结果表明，与正常组织相比，癌组织中的结构结合亚基SA-1显着下调（p <0.01）。 SA-1蛋白在与CRC息肉相邻的受累粘膜中也被下调。在癌组织与正常组织中，内聚负荷蛋白NIPBL也明显低于表达（p <0.01）。直肠粘膜的RNA表达分析表明，在携带增生性腺瘤和腺息肉的患者中，SMC3和SA-1的表达高出两倍，这表明粘着蛋白在整个癌变过程中均差异表达。我们的结果首次证明，内聚失调是人类大肠癌发展的早期事件，并且可能是田间癌变的重要生物标志物。

著录项

  • 作者

    Davis, Ari B.;

  • 作者单位

    Boston University.;

  • 授予单位 Boston University.;
  • 学科 Health Sciences Medicine and Surgery.;Health Sciences General.;Biology Molecular.
  • 学位 M.S.
  • 年度 2014
  • 页码 55 p.
  • 总页数 55
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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