首页> 外文学位 >Overexpression of the receptor tyrosine kinase EphA2 induces malignant transformation of benign mammary epithelia: Implication for increased cell survival and altered cellular adhesions in breast cancer.
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Overexpression of the receptor tyrosine kinase EphA2 induces malignant transformation of benign mammary epithelia: Implication for increased cell survival and altered cellular adhesions in breast cancer.

机译:受体酪氨酸激酶EphA2的过表达诱导了良性乳腺上皮的恶性转化:暗示增加细胞存活率和改变乳腺癌细胞粘附。

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摘要

Tissue function is supported through dynamic and reciprocal communication between cells and the tissue environment. Tyrosine phosphorylation is an important example of a mediator of this communication. Elevated levels of protein tyrosine phosphorylation promote malignant growth and behavior, although the tyrosine kinases that are responsible for this signaling remain largely unknown. Antibodies were generated against tyrosine phosphorylated proteins in malignant tissue in an attempt to identify tyrosine kinases responsible for the malignant phenotype. Here we report increased levels of the EphA2 (ECK) receptor protein tyrosine kinase in clinical specimens and cell models of breast cancer. Overexpression of EphA2 is sufficient to induce malignant transformation and tumorigenesis in non-transformed mammary epithelial cells. Specifically, common in vitro and in vivo assays identified increased survival in a foreign environment and alterations in cell adhesions as phenotypes of the EphA2 transformed cell, MCFEphA2. A major contributor to at least the alteration in cell adhesions provoked by EphA2 overexpression is increased production of the ECM component fibronectin. Further analysis of the balance of cell adhesions in nontransformed tissue reveals that the strength of ECM attachments adversely affects the strength of cell-cell adhesions. Additional studies revealed that the steroid sex hormone estrogen and the transcription factor Myc suppress EphA2 expression. This study depicts EphA2 as a regulator of malignant transformation, which may provide a novel target cancer therapeutics and diagnostics.
机译:通过细胞与组织环境之间的动态和相互通讯来支持组织功能。酪氨酸磷酸化是这种交流介体的重要例子。蛋白质酪氨酸磷酸化水平的升高会促进恶性生长和行为,尽管造成这种信号传导的酪氨酸激酶在很大程度上尚不清楚。产生了针对恶性组织中酪氨酸磷酸化蛋白的抗体,以试图鉴定负责恶性表型的酪氨酸激酶。在这里,我们报告在乳腺癌的临床标本和细胞模型中EphA2(ECK)受体蛋白酪氨酸激酶水平增加。 EphA2的过表达足以在未转化的乳腺上皮细胞中诱导恶性转化和肿瘤发生。具体而言,常见的体外和体内试验确定了外来环境中存活率的提高和细胞粘附的改变,这是EphA2转化细胞MCFEphA2的表型。至少由EphA2过表达引起的细胞粘附改变的主要原因是ECM成分纤连蛋白的产量增加。对未转化组织中细胞粘附平衡的进一步分析表明,ECM附着的强度会对细胞-细胞粘附的强度产生不利影响。其他研究表明,类固醇性激素雌激素和转录因子Myc抑制EphA2表达。这项研究描绘了EphA2作为恶性转化的调节剂,它可能提供一种新型的靶癌症治疗和诊断方法。

著录项

  • 作者

    Zelinski, Daniel Paul.;

  • 作者单位

    Purdue University.;

  • 授予单位 Purdue University.;
  • 学科 Cellular biology.;Oncology.;Molecular biology.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 131 p.
  • 总页数 131
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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