Profiling of pathway-specific changes in gene expression following growth of human cancer cell lines transplanted into mice.
Profiling of pathway-specific changes in gene expression following growth of human cancer cell lines transplanted into mice.
复制标题
DOI：
10.1186/gb-2003-4-7-r46
复制
发表时间：
2003
期刊：
影响因子：
12.3
通讯作者：
Hanash S
中科院分区：
文献类型：
--
作者：
Creighton C;Kuick R;Misek DE;Rickman DS;Brichory FM;Rouillard JM;Omenn GS;Hanash S
癌细胞中基因表达受外在因素调节的程度仍有待确定。根据对人类基因表达的分析，确定了从两种癌细胞系皮下移植到免疫缺陷小鼠中产生的肿瘤的全球基因表达谱，并与培养中生长的细胞系的表达谱进行了比较。体外培养的肿瘤细胞被广泛用于研究癌症的分子生物学和评估对药物和其他试剂的反应。癌细胞中基因表达受外在因素和癌细胞所处微环境调节的程度仍有待确定。将两种癌细胞系（A549肺腺癌和U118胶质母细胞瘤）皮下移植到免疫缺陷小鼠中以形成肿瘤。根据对人类基因表达的分析，确定了肿瘤的总体基因表达谱，并与培养中生长的细胞系的表达谱进行了比较。生物信息学方法将表达水平变化的基因与文献中GO基因注释或MeSH术语定义的功能类别相关联。在体外生长的细胞中以较高水平表达的基因类别表明细胞分裂和代谢增加，反映了细胞增殖的更有利环境。相反，体内肿瘤生长导致细胞外基质（ECM）、细胞粘附、细胞因子和金属内肽酶活性以及新血管形成中涉及的大量基因上调。当置于可比较的组织环境中时，U118细胞和A549细胞表达不同的ECM和细胞粘附相关基因，表明在不同的癌症中细胞外相互作用的不同机制。这种类型的研究使我们能够检查癌细胞对与非癌组织混合的体内肿瘤内基因表达模式的特定贡献。
The full extent to which gene expression in cancer cells is modulated by extrinsic factors remains to be determined. Global gene-expression profiles of tumors produced from two cancer cell lines transplanted subcutaneously into immunodeficient mice were determined, based on analysis of expression of human genes, and compared with expression profiles of the cell lines grown in culture. Tumor cells cultured in vitro are widely used to investigate the molecular biology of cancers and to evaluate responses to drugs and other agents. The full extent to which gene expression in cancer cells is modulated by extrinsic factors and by the microenvironment in which the cancer cells reside remains to be determined. Two cancer cell lines (A549 lung adenocarcinoma and U118 glioblastoma) were transplanted subcutaneously into immunodeficient mice to form tumors. Global gene-expression profiles of the tumors were determined, based on analysis of expression of human genes, and compared with expression profiles of the cell lines grown in culture. A bioinformatics approach associated genes that showed changes in their expression levels with functional classes as defined by either the GO gene annotations or MeSH terms in the literature. The classes of genes expressed at higher levels in cells grown in vitro indicated increased cell division and metabolism, reflecting the more favorable environment for cell proliferation. In contrast, in vivo tumor growth resulted in upregulation of a significant number of genes involved in the extracellular matrix (ECM), cell adhesion, cytokine and metalloendopeptidase activity, and neovascularization. When placed in comparable tissue environments, the U118 cells and the A549 cells expressed different sets of ECM and cell adhesion-related genes, suggesting different mechanisms of extracellular interaction at work in the different cancers. Studies of this type allow us to examine the specific contribution of cancer cells to gene expression patterns within an in vivo tumor mixed with non-cancerous tissue.
登录
查看更多内容
DOI：
10.1073/pnas.95.25.14821
发表时间：
1998-12-08
影响因子：
11.1
作者：
Wang, F;Weaver, VM;Bissell, MJ
通讯作者：
Bissell, MJ
影响因子：
7.5
作者：
Kwiatkowski, DJ
通讯作者：
Kwiatkowski, DJ
影响因子：
64.8
作者：
Clark, EA;Golub, TR;Hynes, RO
通讯作者：
Hynes, RO
影响因子：
82.9
作者：
Beer, DG;Kardia, SLR;Hanash, S
通讯作者：
Hanash, S
影响因子：
6
作者：
Giordano, TJ;Shedden, KA;Hanash, S
通讯作者：
Hanash, S