Overexpression and activation of Akt2 protein in oral squamous cell carcinoma
Overexpression and activation of Akt2 protein in oral squamous cell carcinoma
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DOI：
10.1016/j.oraloncology.2009.06.003
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发表时间：
2009-10-01
期刊：
影响因子：
4.8
通讯作者：
Krisanaprakornkit, Suttichai
中科院分区：
文献类型：
--
作者：
Iamaroon, Anak;Krisanaprakornkit, Suttichai
PI 3 K/Akt信号转导通路的异常在多种肿瘤的发生发展中起着重要作用。正在研究使用靶向PI 3 K/Akt信号通路的新型药物进行口腔癌治疗的高级研究，并取得了可喜的成果。本研究的目的是：（1）通过免疫组织化学方法研究泛Akt及其磷酸化形式（p-Akt）、Akt 1和Akt 2在口腔鳞状细胞癌（OSCC）标本（n = 20）中的表达;（2）确定三种Akt亚型（包括Akt 1、Akt 2和Akt 3）及其各自蛋白的mRNA表达，RT-PCR和Western blot检测5种口腔癌细胞系和正常人口腔角质形成细胞（HOK）的DNA表达。结果显示，泛Akt在80%的OSCC病例中表达，而Akt 1、Akt 2和p-Akt在所有OSCC病例中表达。p-Akt在部分口腔鳞状细胞癌浸润前沿有较强表达。与免疫组化结果一致，p-Akt和Akt 2在所有口腔癌细胞系中过表达，而与HOKs相比，Akt 2 mRNA组成型表达，表明转录后调节。相反，Akt 1 mRNA和蛋白质组成型表达在所有口腔癌细胞系和HOKs，而Akt 3 mRNA似乎是最低限度的表达。总之，这些发现表明，Akt 2和p-Akt在口腔鳞癌中过表达，并可能参与癌变，并建议Akt 2在口腔鳞癌中可能发生转录后修饰。(C)2009爱思唯尔有限公司版权所有。
Aberrations of signal transducers in PI3K/Akt pathway have been found in many human cancers, and may play a critical role in carcinogenesis. Advanced research on oral cancer treatments, using novel agents targeting the PI3K/Akt signaling pathway, is being investigated with promising results. The objectives of this study were (1) to investigate expression of pan-Akt and its phosphorylated form (p-Akt), Akt1, and Akt2 in oral squamous cell carcinoma (OSCC) specimens (n = 20) by immunohistochemistry, and (2) to determine mRNA expression of three Akt isoforms, including Akt1, Akt2, and Akt3, as well as their respective proteins, in five oral cancer cell lines and normal human oral keratinocytes (HOKs) by RT-PCR and Western blot assays. The results show that pan-Akt was expressed in 80% of OSCC cases, while Akt1, Akt2, and p-Akt were expressed in all OSCC cases. An intense expression of p-Akt at the invasive fronts of some OSCC samples was observed. Consistent with the immunohistochemical findings, p-Akt and Akt2 were overexpressed in all oral cancer cell lines in comparison with HOKs, whereas Akt2 mRNA was constitutively expressed, suggesting post-transcriptional regulation. In contrast, Akt1 mRNA and protein were constitutively expressed in all oral cancer cell lines and HOKs, while Akt3 mRNA appeared to be minimally expressed. In summary, these findings demonstrate that Akt2 and p-Akt are overexpressed in OSCC and may be involved in carcinogenesis, and suggest that post-transcriptional modification of Akt2 in OSCC may occur. (C) 2009 Elsevier Ltd. All rights reserved.