Identification of common gene networks responsive to mild hyperthermia in human cancer cells
Identification of common gene networks responsive to mild hyperthermia in human cancer cells
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DOI：
10.3892/ijmm.2013.1366
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发表时间：
2013-07-01
影响因子：
5.4
通讯作者：
Kondo, Takashi
中科院分区：
文献类型：
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作者：
Kariya, Ayako;Tabuchi, Yoshiaki;Kondo, Takashi
热疗（HT）已被用作各种类型恶性肿瘤的可能治疗方式。由于其多效性，它与放疗和/或化疗联合使用已被证明是有益的。然而，细胞对热应激反应的分子机制尚不清楚。因此，本研究的目的是确定人类癌细胞中对轻度HT （MHT）应答的常见基因表达模式。hla人宫颈鳞状细胞癌（SCC）和HSC-3人口腔鳞状细胞癌细胞在41℃下暴露于MHT 30分钟，然后在37℃下培养0-24小时。MHT不影响细胞活力和细胞周期。基因芯片微阵列分析清楚地显示，暴露于MHT后，两种细胞系中许多探针组的表达差异为>= 1.5。在众多差异表达探针组中，发现114个基因在HeLa和HSC-3细胞中均上调，并从共同上调的基因中获得了两个显著的基因网络。基因网络A包括多种热休克蛋白，以及bcl2相关的无氧基因3 (BAG3)，主要与细胞功能和维持的生物学功能相关。基因网络B包括多个抗细胞死亡基因，如早期生长反应1 （EGR1）和内皮素1 (EDN1)，并被发现与细胞死亡和存活的生物学功能相关。实时定量聚合酶链反应表明，所选择的12个基因在4个癌细胞系中的表达模式与芯片数据一致。这些发现可能为癌细胞中MHT反应的详细分子机制提供进一步的见解。
Hyperthermia (HT) has been used as a possible treatment modality for various types of malignant tumors. Due to its pleiotropic effects, its combined use with radiotherapy and/or chemotherapy has proven to be beneficial. However, the molecular mechanisms underling the cellular responses to heat stress remain unclear. Therefore, the aim of this study was to identify common gene expression patterns responsive to mild HT (MHT) in human cancer cells. He La human cervical squamous cell carcinoma (SCC) and HSC-3 human oral SCC cells were exposed to MHT at 41 degrees C for 30 min, followed by culture at 37 degrees C for 0-24 h. MHT did not affect cell viability or the cell cycle. Gene Chip microarray analysis clearly revealed that many probe sets were differentially expressed by a factor of >= 1.5 in both cell lines following exposure to MHT. Of the many differentially expressed probe sets, 114 genes were found to be commonly upregulated in both HeLa and HSC-3 cells, and two significant gene networks were obtained from the commonly upregulated genes. Gene network A included several heat shock proteins, as well as BCL2-associated athanogene 3 (BAG3), and was found to be mainly associated with the biological functions of cellular function and maintenance. Gene network B included several anti-cell death genes, such as early growth response 1 (EGR1) and endothelin 1 (EDN1) and was found to be associated with the biological functions of cell death and survival. Real-time quantitative polymerase chain reaction demonstrated that the gene expression patterns of the 12 genes selected were consistent with the microarray data in four cancer cell lines. These findings may provide further insight into the detailed molecular mechanisms of the MHT response in cancer cells.