Ekizoglu S, Dogan S, Ulker D, Seven D, Gozen E D, Karaman E, Buyru N
Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
Department of Otorhinolaryngology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
Clin Otolaryngol. 2015 Dec;40(6):622-8. doi: 10.1111/coa.12427.
PI3K/Akt signalling pathway is frequently activated in several types of cancer. However, activator molecules have not been analysed systematically in HNSCC. The aim of this study was to investigate upstream activators and inhibitors of this pathway.
Prospective study.
University hospital.
108 patients with HNC who were operated at the Istanbul University, Cerrahpasa Medical Faculty, Department of Otorhinolaryngology.
Mutations in the coding exons and the flanking intronic sequences of the PIK3CA, PIK3R1 and AKT1 genes were analysed by direct sequencing. Expression levels in the tumours and non-cancerous tissue samples were analysed by quantitative RT-PCR, and Western blotting was performed to determine the phosphorylation levels of the Akt1 protein.
Two synonymous alterations in exon 20 of the PIK3CA gene, a 6-bp duplication in the coding region of the PIK3R1 and two different alterations in the non-coding regions of the AKT1 and PIK3R1 genes were observed. Significant downregulation of LKB1 and PTEN mRNA expression levels were detected in tumour tissues compared to non-cancerous tissues. However, we did not observe any difference between the PIK3CA and AKT1 mRNA expression levels in the tumours and non-cancerous tissue samples. Akt1 phosphorylation was increased in 53.57% of the patients.
Our results indicate that the PI3K pathway has an important function in HNSCC progression with the contribution of more than one gene of this pathway. Our data suggest that in a high number of HNSCC tumours, PI3K/Akt signalling is activated by different molecules or by the combination of these molecules.
PI3K/Akt信号通路在多种癌症类型中经常被激活。然而，头颈部鳞状细胞癌（HNSCC）中激活分子尚未得到系统分析。本研究的目的是调查该通路的上游激活剂和抑制剂。
前瞻性研究。
大学医院。
108例在伊斯坦布尔大学塞拉哈帕夏医学院耳鼻喉科接受手术的头颈部癌（HNC）患者。
通过直接测序分析PIK3CA、PIK3R1和AKT1基因编码外显子及其侧翼内含子序列中的突变。通过定量逆转录聚合酶链反应（RT-PCR）分析肿瘤组织和非癌组织样本中的表达水平，并进行蛋白质免疫印迹法以确定Akt1蛋白的磷酸化水平。
观察到PIK3CA基因第20外显子的两个同义改变、PIK3R1编码区的一个6碱基对重复以及AKT1和PIK3R1基因非编码区的两个不同改变。与非癌组织相比，肿瘤组织中LKB1和PTEN mRNA表达水平显著下调。然而，我们未观察到肿瘤组织和非癌组织样本中PIK3CA和AKT1 mRNA表达水平之间存在任何差异。53.57%的患者Akt1磷酸化增加。
我们的结果表明，PI3K通路在HNSCC进展中具有重要作用，该通路的多个基因均有贡献。我们的数据表明，在大量HNSCC肿瘤中，PI3K/Akt信号由不同分子或这些分子的组合激活。
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