Yanai Yoshiaki, Micallef Mark J, Yamamoto Shigeto, Yamamoto Kozou, Yamauchi Hiroshi, Ikegami Hakuo, Kurimoto Masashi
Hayashibara Biochemical Laboratories Inc., Fujisaki Institute, Fujisaki 675-1, Okayama 702-8006, Japan.
Anticancer Res. 2003 May-Jun;23(3B):2339-48.
The induction of genes associated with cellular apoptosis by tumor necrosis factor-alpha (TNF-alpha) in human cancer cell line sof various tissue origins may characterize TNF-alpha responder cell lines/cancers.
Using quantitative real-time polymerase chain reaction (PCR), the comprehensive molecular profiling of genes downstream of the TNF-alpha receptor genes in 91 well-defined human cancer cell lines allowed us to elucidate relationships between TNF-alpha response and the genetic expression profiles of the target cell lines.
Among the 52 genes tested, the above average expression of Akt mRNA showed significant correlation with TNF-alpha-induced susceptibility to apoptosis. In addition, multidrug resistance protein 5 (MRP5) and tumor necrosis factor receptor type 1 (TNFR1) mRNA expressions also appear to be possible markers for responsiveness to TNF-alpha.
These results provide a preliminary basis for the screening for genetic markers that may help to predict a favorable therapeutic outcome, and also to identify patients who may benefit from cytokine therapy.
肿瘤坏死因子-α(TNF-α)在各种组织来源的人类癌细胞系中诱导与细胞凋亡相关的基因,这可能是TNF-α反应性细胞系/癌症的特征。
使用定量实时聚合酶链反应(PCR),对91个明确的人类癌细胞系中TNF-α受体基因下游的基因进行全面分子谱分析,使我们能够阐明TNF-α反应与靶细胞系基因表达谱之间的关系。
在所检测的52个基因中,Akt mRNA的高于平均水平的表达与TNF-α诱导的凋亡敏感性显著相关。此外多药耐药蛋白5(MRP5)和肿瘤坏死因子受体1型(TNFR1)mRNA表达似乎也是对TNF-α反应性的可能标志物。
这些结果为筛选可能有助于预测良好治疗结果的遗传标志物提供了初步依据,也有助于识别可能从细胞因子治疗中受益的患者。