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首页> 外文学位 >Selective utilization of ectopic epidermal growth factor receptor signaling in estrogen receptor positive breast cancer cells.
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Selective utilization of ectopic epidermal growth factor receptor signaling in estrogen receptor positive breast cancer cells.

机译：雌激素受体阳性乳腺癌细胞中异位表皮生长因子受体信号的选择性利用。

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摘要

Overexpression of the transmembrane tyrosine kinase epidermal growth factor receptor (EGFR) correlates with absence of estrogen receptor (ER) and poor prognosis in breast cancer, suggesting that this molecule may play a role in escape from dependence on estrogen for growth. To test this hypothesis, we have stably transfected the human EGFR into two ER positive human breast cancer cell lines, MCF-7 cells and a clone of MCF-7 cells previously transfected with the EGFR ligand transforming growth factor alpha.;Expression of the EGFR is modulated in vitro in both cell lines in response to culture conditions. Cells maintain elevated transfected EGFR expression upon estrogen withdrawal, but growth in medium containing estrogen results in loss of expression at the level of both protein and messenger RNA. Although the transfected DNA is not lost, long-term growth in the presence of estrogen is associated with hypermethylation of the integrated plasmid. Loss of expression is not a consequence of nonspecific repression of the heterologous promoter. Changes in EGFR expression are reversible, implying that this phenomenon occurs in response to environmental conditions.;Transfected cells retain ER expression as well as the ability to induce estrogen-responsive genes upon hormone treatment, indicating that the EGFR overexpression does not interfere with ER function. Growth of cells overexpressing EGFR in the absence of estrogen is enhanced compared to control transfectants; however, growth in the presence of estrogen is inhibited. This effect may be mediated through induction of polypeptide factors capable of binding EGFR, because EGFR ligands inhibit growth of EGFR overexpressing cells. These results suggest that overexpression of EGFR in the absence of estrogen confers a selective advantage upon cells but is deleterious when estrogen is present.;The instability of EGFR expression in the presence of estrogen has complicated study of the interactions between these two pathways. In an attempt to develop a system that may be useful in delineating the interactions between ER and EGFR in future studies, an inducible gene expression system controlled by tetracycline was used to regulate expression of the EGFR-related c-erbB-2 gene in MCF-7 cells.
机译：跨膜酪氨酸激酶表皮生长因子受体（EGFR）的过度表达与雌激素受体（ER）的缺乏和乳腺癌的预后不良有关，表明该分子可能在逃避对雌激素生长的依赖中发挥作用。为了验证这一假设，我们已将人类EGFR稳定转染到两个ER阳性人类乳腺癌细胞系MCF-7细胞和先前已被EGFR配体转化生长因子α转染的MCF-7细胞克隆中。响应于培养条件，在两种细胞系中均在体外调节β-内化酶。雌激素撤出后，细胞可维持转染的EGFR表达升高，但在含有雌激素的培养基中生长会导致蛋白质和信使RNA水平的表达丧失。尽管转染的DNA没有丢失，但是在雌激素存在下的长期生长与整合质粒的高甲基化有关。表达的丧失不是异源启动子非特异性抑制的结果。 EGFR表达的变化是可逆的，表明这种现象是在环境条件下发生的。转染的细胞保留ER表达以及激素治疗后诱导雌激素反应性基因的能力，这表明EGFR的过表达不会干扰ER功能。 。与对照转染子相比，在没有雌激素的情况下，过表达EGFR的细胞的生长得以增强；但是，在雌激素存在下生长受到抑制。这种作用可能是通过诱导能够结合EGFR的多肽因子来介导的，因为EGFR配体会抑制EGFR过表达细胞的生长。这些结果表明在缺乏雌激素的情况下EGFR的过表达赋予细胞选择性的优势，但是在存在雌激素的情况下是有害的。在雌激素存在下EGFR表达的不稳定性使这两种途径之间的相互作用的研究变得复杂。为了开发一种可能在未来研究中描述ER和EGFR之间相互作用的系统，使用了由四环素控制的诱导型基因表达系统来调节MCF-中EGFR相关c-erbB-2基因的表达。 7个单元格。

著录项

  • 作者

    Miller, David Lee.;

  • 作者单位

    Georgetown University Medical Center.;

  • 授予单位 Georgetown University Medical Center.;
  • 学科 Molecular biology.;Oncology.;Cellular biology.
  • 学位 Ph.D.
  • 年度 1996
  • 页码 195 p.
  • 总页数 195
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 无线电电子学、电信技术;
  • 关键词

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