Phosphorylation status of Akt and caspase-9 in gastric and colorectal carcinomas.
Phosphorylation status of Akt and caspase-9 in gastric and colorectal carcinomas.
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发表时间：
2014-05
影响因子：
1.4
通讯作者：
Akiko Sangawa;M. Shintani;N. Yamao;S. Kamoshida
中科院分区：
文献类型：
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作者：
Akiko Sangawa;M. Shintani;N. Yamao;S. Kamoshida
丝氨酸/苏氨酸蛋白激酶B/Akt在涉及转录调节、细胞存活和凋亡的多个信号转导过程的协调中起核心作用。Akt激酶的激活是几种类型癌症的预后因素;然而，其在胃肠道癌症中的作用尚未完全了解。胱天蛋白酶-9是Akt底物，其属于蛋白酶的胱天蛋白酶家族，其作为线粒体凋亡途径的引发剂起作用。关于caspase-9磷酸化的作用知之甚少，其下调了该酶的凋亡活性。本研究旨在探讨磷酸化（p）-Akt和磷酸化（p）-caspase-9在胃癌和结直肠癌中的表达及其与胃癌和结直肠癌患者临床病理参数的关系。通过免疫组织化学分析了75例晚期胃腺癌（37例高至中等分化和38例低分化）和76例晚期结直肠腺癌（69例高至中等分化和7例低分化）的p-Akt和p-caspase-9表达。我们的研究结果揭示了p-Akt和p-caspase-9在胃癌和结直肠癌中表达的相关性。p-caspase-9在结直肠癌中的表达水平显著高于胃癌，表明肿瘤特异性调节。虽然p-Akt/p-caspase-9信号转导的生物学作用尚不清楚，但我们认为caspase-9的磷酸化可能是评估胃肠癌状态和抗癌治疗效果的有用工具。
The serine/threonine protein kinase B/Akt plays a central role in the coordination of multiple signal transduction processes involved in transcriptional regulation, cell survival, and apoptosis. Activation of Akt kinase is a prognostic factor in several types of cancers; however, its role in gastrointestinal cancers is not fully understood. Caspase-9 is an Akt substrate that belongs to the caspase family of proteases, which function as initiators of the mitochondrial apoptotic pathway. Little is known about the role of caspase-9 phosphorylation, which downregulates the apoptotic activity of the enzyme. In this study, we investigated the expression of phosphorylated (p)-Akt and phosphorylated (p)-caspase-9 in gastric and colorectal carcinoma and the relationship between p-Akt and p-caspase-9 expression and clinicopathological parameters of gastric and colorectal cancer patients. In total, 75 samples of advanced gastric adenocarcinoma (37 well-to-moderately differentiated and 38 poorly differentiated) and 76 samples of advanced colorectal adenocarcinoma (69 well-to-moderately differentiated and 7 poorly differentiated) were analyzed for p-Akt and p-caspase-9 expression by immunohistochemistry. Our results reveal a correlation between p-Akt and p-caspase-9 expression in gastric and colorectal cancers. Levels of p-caspase-9 were significantly higher in colorectal cancer than in gastric cancer, indicating tumor-specific regulation. Although the biological role of p-Akt/p-caspase-9 signaling remains unclear, we suggest that phosphorylation of caspase-9 may be a useful tool to assess the state of gastrointestinal cancer and the effects of anti-cancer therapy.