The influence of tumor size and environment on gene expression in commonly used human tumor lines.
The influence of tumor size and environment on gene expression in commonly used human tumor lines.
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DOI：
10.1186/1471-2407-4-35
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发表时间：
2004-07-15
期刊：
影响因子：
3.8
通讯作者：
Leopold WR
中科院分区：
文献类型：
--
作者：
Gieseg MA;Man MZ;Gorski NA;Madore SJ;Kaldjian EP;Leopold WR
尽管固体肿瘤模型被广泛用于开发抗癌药物，但对它们在啮齿动物体内的表达谱研究还很少。我们已经使用Affymetrix U95A GeneChips应用RNA表达谱来解决关于人类肿瘤株的基本生物学问题。为了确定基因表达是否随着肿瘤大小的增加而显著变化，我们分析了两个人结肠癌株(Colo205和HCT-116)三个不同大小(200 mg、500 mg和1000 mg)的样本。为了研究小鼠品系对基因表达的影响，还比较了C.B-17SCID和NU/NU小鼠的肿瘤标本。最后，通过比较在两种环境下生长的品系的基因表达谱，研究了组织培养和体内样品之间的基因表达差异。多维标度和方差分析表明，肿瘤株之间存在显著差异，随着肿瘤大小的增加，基因表达保持不变。统计分析表明，由于生长肿瘤的小鼠品系的原因，63个基因有差异表达，但编码蛋白的功能与任何不同的生物途径无关。组织培养和异种移植样本的等级聚类表明，对于每个单独的肿瘤株，体内和体外的轮廓彼此比任何其他轮廓更相似。我们在异种移植样本中发现了36个高表达的基因，这些基因编码了涉及细胞外基质、细胞表面受体和转录因子的蛋白。另有17个基因在组织培养样本中高表达，并编码了与细胞分裂、细胞周期和RNA产生有关的蛋白质。肿瘤生长的环境对基因表达有显着影响，但肿瘤大小对皮下生长的实体瘤影响很小或没有影响。此外，单个肿瘤株有一种RNA表达模式，即使在不同的环境中生长，也能清楚地将其与其他株系区分开来。这可作为临床前肿瘤学研究的质量控制工具。
The expression profiles of solid tumor models in rodents have been only minimally studied despite their extensive use to develop anticancer agents. We have applied RNA expression profiling using Affymetrix U95A GeneChips to address fundamental biological questions about human tumor lines. To determine whether gene expression changed significantly as a tumor increased in size, we analyzed samples from two human colon carcinoma lines (Colo205 and HCT-116) at three different sizes (200 mg, 500 mg and 1000 mg). To investigate whether gene expression was influenced by the strain of mouse, tumor samples isolated from C.B-17 SCID and Nu/Nu mice were also compared. Finally, the gene expression differences between tissue culture and in vivo samples were investigated by comparing profiles from lines grown in both environments. Multidimensional scaling and analysis of variance demonstrated that the tumor lines were dramatically different from each other and that gene expression remained constant as the tumors increased in size. Statistical analysis revealed that 63 genes were differentially expressed due to the strain of mouse the tumor was grown in but the function of the encoded proteins did not link to any distinct biological pathways. Hierarchical clustering of tissue culture and xenograft samples demonstrated that for each individual tumor line, the in vivo and in vitro profiles were more similar to each other than any other profile. We identified 36 genes with a pattern of high expression in xenograft samples that encoded proteins involved in extracellular matrix, cell surface receptors and transcription factors. An additional 17 genes were identified with a pattern of high expression in tissue culture samples and encoded proteins involved in cell division, cell cycle and RNA production. The environment a tumor line is grown in can have a significant effect on gene expression but tumor size has little or no effect for subcutaneously grown solid tumors. Furthermore, an individual tumor line has an RNA expression pattern that clearly defines it from other lines even when grown in different environments. This could be used as a quality control tool for preclinical oncology studies.