Nakamura Toru, Fidler Isaiah J, Coombes Kevin R
Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77230, USA.
Cancer Res. 2007 Jan 1;67(1):139-48. doi: 10.1158/0008-5472.CAN-06-2563.
To determine the influence of the microenvironment on changes in gene expression, we did microarray analysis on three variant lines of a human pancreatic cancer (FG, L3.3, and L3.6pl) with different metastatic potentials. The variant lines were grown in tissue culture in the subcutis (ectopic) or pancreas (orthotopic) of nude mice. Compared with tissue culture, the number of genes of which the expression was affected by the microenvironment was up-regulated in tumors growing in the subcutis and pancreas. In addition, highly metastatic L3.6pl cells growing in the pancreas expressed significantly higher levels of 226 genes than did the L3.3 or FG variant cells. Growth of the variant lines in the subcutis did not yield similar results, indicating that the orthotopic microenvironment significantly influences gene expression in pancreatic cancer cells. These data suggest that investigations of the functional consequence of gene expression require accounting for experimental growth conditions.
为了确定微环境对基因表达变化的影响，我们对具有不同转移潜能的人胰腺癌的三个变异株系（FG、L3.3和L3.6pl）进行了微阵列分析。这些变异株系在裸鼠皮下（异位）或胰腺（原位）的组织培养中生长。与组织培养相比，在皮下和胰腺中生长的肿瘤中，其表达受微环境影响的基因数量上调。此外，在胰腺中生长的高转移性L3.6pl细胞比L3.3或FG变异细胞表达226个基因的水平显著更高。变异株系在皮下生长未产生类似结果，表明原位微环境显著影响胰腺癌细胞中的基因表达。这些数据表明，对基因表达功能后果的研究需要考虑实验生长条件。
