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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Defined factors induce reprogramming of gastrointestinal cancer cells
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Defined factors induce reprogramming of gastrointestinal cancer cells

机译：明确的因素诱导胃肠道癌细胞重编程

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摘要

Although cancer is a disease with genetic and epigenetic origins, the possible effects of reprogramming by defined factors remain to be fully understood. We studied the effects of the induction or inhibition of cancer-related genes and immature status-related genes whose alterations have been reported in gastrointestinal cancer cells. Retroviral-mediated introduction of induced pluripotent stem (IPS) cell genes was necessary for inducing the expression of immature status-related proteins, including Nanog, Ssea4, Tra-1-60, and Tra-1-80 in esophageal, stomach, colorectal, liver, pancreatic, and cholangiocellular cancer cells. Induced cells, but not parental cells, possessed the potential to express morphological patterns of ectoderm, mesoderm, and endoderm, which was supported by epigenetic studies, indicating methylation of DNA strands and the histone H3 protein at lysine 4 in promoter regions of pluripotency-associated genes such as NANOG. In in vitro analysis induced cells showed slow proliferation and were sensitized to differentiation-inducing treatment, and in vivo tumorigenesis was reduced in NOD/SCID mice. This study demonstrated that pluripotency was manifested in induced cells, and that the induced pluripotent cancer (iPC) cells were distinct from natural cancer cells with regard to their sensitivity to differentiation-inducing treatment. Retroviral-mediated introduction of iPC cells confers higher sensitivity to chemotherapeutic agents and differentiation-inducing treatment.
机译：尽管癌症是一种具有遗传和表观遗传起源的疾病，但是通过明确的因素进行重编程的可能影响仍有待充分了解。我们研究了诱导或抑制癌症相关基因和未成熟状态相关基因的影响，这些基因的改变已在胃肠道癌细胞中被报道。逆转录病毒介导的诱导性多能干（IPS）细胞基因的引入对于诱导未成熟状态相关蛋白（包括Nanog，Ssea4，Tra-1-60和Tra-1-80）在食道，胃，结直肠中的表达是必要的，肝，胰腺和胆管癌细胞。诱导细胞而非亲代细胞具有表达外胚层，中胚层和内胚层形态模式的潜力，这受到表观遗传学研究的支持，表明多能性相关启动子区域中的DNA链和赖氨酸4处的组蛋白H3蛋白甲基化。基因如NANOG。在体外分析中，诱导的细胞显示出缓慢的增殖，并且对诱导分化的治疗敏感，并且在NOD / SCID小鼠体内的体内肿瘤发生减少。这项研究表明，多能性在诱导细胞中表现出来，并且诱导多能性癌细胞（iPC）在分化诱导治疗方面的敏感性不同于天然癌细胞。逆转录病毒介导的iPC细胞的引入赋予对化疗药物和诱导分化的治疗更高的敏感性。

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  • 作者

    Norikatsu Miyoshi; Hideshi lshii; Ken-ichi Nagai; Hiromitsu Hoshino; Koshi Mimori; Fumiaki Tanaka; Hiroaki Nagano; Mitsugu Sekimoto; Yuichiro Doki; Masaki Mori;

  • 作者单位

    Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;

    Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan Department of Molecular and Cellular Biology, Division of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Ohita 874-0838, Japan;

    Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;

    Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;

    Department of Molecular and Cellular Biology, Division of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Ohita 874-0838, Japan;

    Department of Molecular and Cellular Biology, Division of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Ohita 874-0838, Japan;

    Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;

    Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;

    Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan;

    Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan Department of Molecular and Cellular Biology, Division of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Ohita 874-0838, Japan;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cancer stem cells; epigenetics; pluripotent stem cells; embryonic stem cells; differentiation;

    机译：癌症干细胞表观遗传学多能干细胞;胚胎干细胞;差异化;

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