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首页> 外文学位 >Distinct roles for members of the trk neurotrophin receptor family in the biology of medullary thyroid carcinoma.
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Distinct roles for members of the trk neurotrophin receptor family in the biology of medullary thyroid carcinoma.

机译：trk神经营养蛋白受体家族成员在甲状腺髓样癌生物学中的不同作用。

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摘要

Medullary thyroid carcinoma (MTC) is a neoplasm of the C-cells of the thyroid. Patients who have a genetic predisposition to develop MTC provide a model to study MTC progression. This progression can include development of an aggressive, metastatic disease that ultimately kills the patient. The goal of this thesis is to determine what molecular events may underlie the development and progression of MTC tumors by investigating a potential role for the trk family of neurotrophin receptors.;To begin this work, I evaluated trkC as a candidate gene for inherited forms of MTC by cloning the human homolog of trkC and mapping it to chromosome 15q24-q25. It is not the gene responsible for inherited MTC, which maps to chromosome 10 and is now known to be the ret proto-oncogene.;To further investigate a role for the trk family in MTC, immuno-histochemical analyses were performed. The trkB neurotrophin receptor was expressed in normal and hyperplastic C-cells and this expression was diminished in MTC. In contrast, expression of the trkC neurotrophin receptor was never detected in normal C-cells, but demonstrated increasing staining with tumor development, including markedly strong staining in the cells of the most aggressive tumors. The trkA neurotrophin receptor demonstrated no staining in normal C-cells and variable levels of staining in the progression of MTC.;In the context of these in vivo expression patterns, a cell culture model was developed. Expression and activation of trkA or trkC in a cultured MTC line resulted in increased cell growth in vitro and increased tumor growth when the expressing cells were injected into nude mice. In contrast, although the cells expressing trkB demonstrated increased cell growth in vitro, little to no tumor development occurred when the trkB expressing cells were injected into nude mice. These results suggest a model for tumor development of MTC in which loss of growth control due to a decrease in expression of one trk family member, trkB, along with a gain in growth potential by an increase in the expression of a different trk family member, trkC, are critical events in tumor initiation, tumor progression, or both.
机译：甲状腺髓样癌（MTC）是甲状腺C细胞的肿瘤。具有发展MTC的遗传倾向的患者提供了研究MTC进展的模型。这种进展可能包括侵略性转移性疾病的发展，最终杀死患者。本论文的目的是通过研究神经营养蛋白受体trk家族的潜在作用来确定哪些分子事件可能是MTC肿瘤发生和发展的基础。为了开始这项工作，我将trkC评估为遗传形式的tkC的候选基因。通过克隆trkC的人类同源物并将其映射到15q24-q25染色体上来进行MTC。它不是负责遗传MTC的基因，它映射到10号染色体，现在被称为ret原癌基因。为了进一步研究trk家族在MTC中的作用，进行了免疫组织化学分析。 trkB神经营养蛋白受体在正常和增生性C细胞中表达，而该表达在MTC中减弱。相反，在正常C细胞中从未检测到trkC神经营养蛋白受体的表达，但是随着肿瘤的发展，染色表现出增加的染色，包括在最具侵袭性的肿瘤细胞中明显染色。 trkA神经营养蛋白受体在正常C细胞中无染色，在MTC进程中无变化。在这些体内表达方式的背景下，建立了细胞培养模型。当将表达细胞注射到裸鼠中时，培养的MTC系中trkA或trkC的表达和激活导致体外细胞生长增加和肿瘤生长增加。相反，尽管表达trkB的细胞在体外显示出增加的细胞生长，但是当将表达trkB的细胞注射到裸鼠中时几乎没有发生肿瘤的发展。这些结果提示了一种MTC肿瘤发展的模型，其中，由于一个trk家族成员trkB的表达减少而导致的生长控制丧失，以及由于另一个trk家族成员的表达增加而导致的生长潜力的增加， trkC是肿瘤引发，肿瘤进展或两者中的关键事件。

著录项

  • 作者

    McGregor, Lisa MacNabb.;

  • 作者单位

    The Johns Hopkins University.;

  • 授予单位 The Johns Hopkins University.;
  • 学科 Cellular biology.;Genetics.;Neurosciences.;Oncology.
  • 学位 Ph.D.
  • 年度 1998
  • 页码 129 p.
  • 总页数 129
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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