Effect of connective tissue growth factor on hypoxia-inducible factor 1α degradation and tumour angiogenesis
Effect of connective tissue growth factor on hypoxia-inducible factor 1α degradation and tumour angiogenesis
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DOI：
10.1093/jnci/djj242
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发表时间：
2006-07-19
影响因子：
10.3
通讯作者：
Kuo, Min-Liang
中科院分区：
文献类型：
--
作者：
Chang, Cheng-Chi;Lin, Ming-Tsai;Kuo, Min-Liang
背景：结缔组织生长因子（CTGF）抑制小鼠模型中人肺癌细胞的转移活性；然而，这种调节的机制尚不清楚。我们研究了血管生成在此过程中的作用。方法：用含有CTGF或缺氧诱导因子(HIF)1a的载体或载体对照稳定转染CL1-5和A549人肺腺癌细胞。将转染的细胞注射到裸鼠体内（每组n = 10），并测量肿瘤生长、转移和小鼠存活率。使用内皮细胞标记物 CD31 和 CTGF 的抗体对切除的异种移植肿瘤和原发性人肺腺癌 (n = 24) 进行免疫组织化学分析。通过报告基因检测体外评估 HIF-1 α 和血管内皮生长因子 (VEGF) A 的表达。用 HIF-1 α 突变体和反义阻滞缺陷蛋白 1 (ARD-1) 瞬时转染细胞，并通过免疫沉淀法测定 HIF-1 α 乙酰化。所有统计检验都是双面的。结果：来自 CTGF 转染子的异种移植肿瘤比来自对照转染细胞的异种移植肿瘤生长得更慢，并且 HIF-1a 和 VEGF-A 的表达、血管化（通过 CD31 表达评估）和转移（所有 P
Background: Connective tissue growth factor (CTGF) inhibits the metastatic activity of human lung cancer cells in a mouse model; however, the mechanism of this modulation is unclear. We investigated the role of angiogenesis in this process. Methods: CL1-5 and A549 human lung adenocarcinoma cells were stably transfected with vectors containing CTGF or hypoxia-inducible factor (HIF) la or with vector controls. Transfected cells were injected into nude mice (n = 10 per group), and tumor growth, metastasis, and mouse survival were measured. Excised xenograft tumors and primary human lung adenocarcinomas (n = 24) were subjected to immunohistochemistry with antibodies to the endothelial cell marker CD31 and to CTGF. Expression of HIF-1 alpha and vascular endothelial growth factor (VEGF) A was assessed in vitro by using reporter gene assays. Cells were transiently transfected with HIF-1 alpha mutant and antisense arrest-defective 1 protein (ARD-1), and HIF-1 alpha acetylation was assayed by immunoprecipitation. All statistical tests were two-sided. Results: Xenograft tumors derived from CTGF transfectants grew more slowly than those from control-transfected cells and had reduced expression of HIF-1a and VEGF-A, vascularization (as assessed by CD31 expression), and metastasis (all P