Skubitz Keith M, Cheng Edward Y, Clohisy Denis R, Thompson Roby C, Skubitz Amy P N
Department of Medicine, University of Minnesota Medical School, Minneapolis, USA.
J Lab Clin Med. 2004 Oct;144(4):193-200. doi: 10.1016/j.lab.2004.06.005.
Malignant transformation is thought to be associated with changes in the expression of a number of genes, and this alteration in gene expression is considered critical to the development of the malignant phenotype. In this study, gene expression in 8 samples of giant-cell tumor (GCT) of bone, as well as in bone at the site of osteoarthritis and in a variety of normal tissues, was determined at Gene Logic Inc (Gaithersburg, Md) with the use of Affymetrix GeneChip U_133 arrays containing approximately 40,000 genes/expressed sequence tags (ESTs). Gene-expression analysis was performed with the use of the Gene Logic GeneExpress Software System. Differences in gene expression between GCTs and bone were observed. In addition, genes expressed uniquely in GCTs among these and 519 samples from 20 other tissue types were identified. Some of the genes that were found to be overexpressed in GCTs, such as tartrate-resistant acid phosphatase and the lysosomal H + -transporting ATPase, are also expressed by osteoclasts. Osteoprotegrin ligand (OPGL) was also selectively overexpressed in GCTs. The genes found to be overexpressed in GCTs appear to reflect the genetic profile of osteoclast-lineage cells and also the genetic profile of an osteoclastogenic environment. The genes identified in this study may play a role in the pathogenesis of GCTs, confirm the likely importance of OPGL in GCT pathogenesis, and may indicate other possible targets to which antitumor therapy could be directed.
恶性转化被认为与许多基因表达的变化有关，而这种基因表达的改变被认为对恶性表型的发展至关重要。在本研究中，使用包含约40,000个基因/表达序列标签（EST）的Affymetrix GeneChip U_133阵列，在Gene Logic公司（马里兰州盖瑟斯堡）测定了8例骨巨细胞瘤（GCT）样本以及骨关节炎部位的骨组织和多种正常组织中的基因表达。使用Gene Logic GeneExpress软件系统进行基因表达分析。观察到GCT与骨组织之间的基因表达差异。此外，还在这些样本以及来自其他20种组织类型的519个样本中鉴定出了在GCT中独特表达的基因。一些在GCT中被发现过度表达的基因，如抗酒石酸酸性磷酸酶和溶酶体H⁺转运ATP酶，也由破骨细胞表达。骨保护素配体（OPGL）在GCT中也选择性地过度表达。在GCT中发现过度表达的基因似乎反映了破骨细胞谱系细胞的基因特征以及破骨细胞生成环境的基因特征。本研究中鉴定出的基因可能在GCT的发病机制中起作用，证实了OPGL在GCT发病机制中的可能重要性，并可能指出抗肿瘤治疗可以针对的其他可能靶点。
