ROLE OF PDGF EXPRESSSION IN THE NEOPLASTIC PROCESS

PDGF 表达在肿瘤形成过程中的作用

• 批准号: 3916898
• 负责人: M PECH
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3916898
• 关键词: RNA; gene expression; genetic manipulation; genetic promoter element; genetic translation; genetically modified animals; growth factor receptors; human immunodeficiency virus 1; laboratory mouse; neoplastic transformation; platelet derived growth factor; protein structure; transposon /insertion element

The human platelet-derived growth factor (PDGF) is one of several known growth factors involved in the regulation of cell proliferation. PDGF is composed of two polypeptide chains. PDGF- 1 and PDGF-2. One or both of these chains can be found in a number of human tumor cells which also express the PDGF receptor. The deregulation of PDGF expression might confer a growth advantage to those cells by autocrine stimulation and contribute to the malignant phenotype. We have started to investigate which mechanisms regulate PDGF expression in tumor versus normal cells. In addition, we wanted to know how a high level of PDGF expression would affect normal diploid cells or the complete organism. We found that PDGF-1 differs in its expression pattern from PDGF-2. PDGF-2 expression is controlled at three different levels. The PDGF-2 promoter, which was identified and dissected into its different regulatory elements, is one target for control in normal and tumor cells: other levels of regulation are posttranscriptional and include inhibition of translation by secondary RNA structures. A high expression of PDGF-2 gave rise to polyclonal tumors in mice injected with a retrovirus containing the normal PDGF-2 gene. Experiments with transgenic mice have been initiated to introduce the human genes for PDGF-1 and -2 into the germ line and study effects of their overexpression.

人血小板衍生生长因子（PDGF）是几种 已知的参与细胞生长调节的生长因子 增殖 PDGF由两条多肽链组成。PDGF- 1和PDGF-2。 这些链中的一个或两个可以在一些 也表达PDGF受体的人类肿瘤细胞。 的 PDGF表达的失调可能会赋予生长优势， 这些细胞通过自分泌刺激， 恶性表型 我们已经开始调查 与正常细胞相比，肿瘤细胞中的PDGF表达调节机制。 此外，我们想知道高水平的PDGF表达是如何在 会影响正常的二倍体细胞或整个生物体 我们 发现PDGF-1的表达模式与PDGF-2不同。 PDGF-2表达控制在三个不同水平。 的 PDGF-2启动子，该启动子被鉴定并分解成其 不同的调节元件，是正常情况下控制的一个目标， 和肿瘤细胞：其他水平的调控是转录后的 并且包括通过二级RNA结构抑制翻译。 PDGF-2的高表达引起小鼠多克隆肿瘤 注射含有正常PDGF-2基因的逆转录病毒。 转基因小鼠的实验已经启动，以引入 人类PDGF-1和PDGF-2基因进入生殖细胞系的研究 其过度表达的影响。