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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Specific induction of tumor neovasculature death by modified murine PPE-1 promoter armed with HSV-TK.
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Specific induction of tumor neovasculature death by modified murine PPE-1 promoter armed with HSV-TK.

机译：携带HSV-TK的改良鼠PPE-1启动子特异性诱导肿瘤新血管死亡。

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摘要

BACKGROUND: One strategy to increase tissue specificity of gene therapy is to use promoters or enhancers. OBJECTIVES: (1) To enhance the selectivity of a murine preproendothelin-1 (PPE-1) promoter in tumor angiogenesis by using a positive endothelial transcription-binding element. (2) To test the specificity and efficiency of the modified PPE-1 promoter [PPE-1(3X)] in vitro and in vivo by using reporter genes, and the therapeutic gene herpes simplex virus-thymidine kinase (HSV-TK) in a mouse model of Lewis lung carcinoma (LLC). RESULTS: The modified PPE-1 promoter specifically induced expression in the tumor angiogenic vascular bed with a 35-fold higher expression compared to the normal vasculare bed of the lung. Thus, when the HSV-TK gene controlled by the modified PPE-1 promoter was used systemically, it induced tumor-specific necrosis, apoptosis and mononuclear infiltrates, leading to massive destruction of the neovasculature of the pulmonary metastasis, which suppressed metastasis development. CONCLUSIONS: These results show that an adenoviral vector armed with HSV-TK controlled by the endothelial-selective murine PPE-1(3X) promoter is efficient and safe to target tumor neovasculature.
机译：背景：增加基因治疗的组织特异性的一种策略是使用启动子或增强子。目的：（1）通过使用一种积极的内皮转录结合元件来增强鼠前内皮素-1（PPE-1）启动子在肿瘤血管生成中的选择性。 （2）使用报道基因和治疗基因疱疹单纯疱疹病毒胸苷激酶（HSV-TK）在体外和体内测试修饰的PPE-1启动子[PPE-1（3X）]的特异性和效率。 Lewis肺癌（LLC）的小鼠模型。结果：修饰的PPE-1启动子特异性诱导肿瘤血管生成血管床中的表达，其表达比正常肺血管床高35倍。因此，当全身使用由修饰的PPE-1启动子控制的HSV-TK基因时，它会诱导肿瘤特异性坏死，凋亡和单核浸润，从而导致肺转移的新血管大量破坏，从而抑制了转移的发展。结论：这些结果表明，由内皮选择性鼠PPE-1（3X）启动子控制的，带有HSV-TK的腺病毒载体可有效，安全地靶向肿瘤新脉管系统。

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